Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy
Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFN...
Ausführliche Beschreibung
Autor*in: |
Sckisel, Gail D. [verfasserIn] |
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E-Artikel |
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Englisch |
Erschienen: |
2017 |
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Anmerkung: |
© The Author(s). 2017 |
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Übergeordnetes Werk: |
Enthalten in: Journal for ImmunoTherapy of Cancer - London : BioMed Central, 2013, 5(2017), 1 vom: 18. Apr. |
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Übergeordnetes Werk: |
volume:5 ; year:2017 ; number:1 ; day:18 ; month:04 |
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DOI / URN: |
10.1186/s40425-017-0235-4 |
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Katalog-ID: |
SPR036435600 |
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520 | |a Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. Results Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to $ CD62L^{low} $ (T effector/effector memory,$ T_{E/EM} $) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on $ T_{E/EM} $ cells was observed in patients undergoing systemic high-dose IL-2 therapy. Conclusions These data highlight PD-1 expressing and/or $ T_{E/EM} $ subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. Trial registration ClinicalTrials.gov NCT01416831. Registered August 12, 2011. | ||
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700 | 1 | |a Monjazeb, Arta M. |4 aut | |
700 | 1 | |a Murphy, William J. |4 aut | |
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10.1186/s40425-017-0235-4 doi (DE-627)SPR036435600 (SPR)s40425-017-0235-4-e DE-627 ger DE-627 rakwb eng Sckisel, Gail D. verfasserin aut Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. Results Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to $ CD62L^{low} $ (T effector/effector memory,$ T_{E/EM} $) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on $ T_{E/EM} $ cells was observed in patients undergoing systemic high-dose IL-2 therapy. Conclusions These data highlight PD-1 expressing and/or $ T_{E/EM} $ subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. Trial registration ClinicalTrials.gov NCT01416831. Registered August 12, 2011. Immunotherapy (dpeaa)DE-He213 Cancer (dpeaa)DE-He213 PD-1 (dpeaa)DE-He213 Bystander Activation (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 NKG2D (dpeaa)DE-He213 Mirsoian, Annie aut Minnar, Christine M. aut Crittenden, Marka aut Curti, Brendan aut Chen, Jane Q. aut Blazar, Bruce R. aut Borowsky, Alexander D. aut Monjazeb, Arta M. aut Murphy, William J. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 18. Apr. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:18 month:04 https://dx.doi.org/10.1186/s40425-017-0235-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 18 04 |
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10.1186/s40425-017-0235-4 doi (DE-627)SPR036435600 (SPR)s40425-017-0235-4-e DE-627 ger DE-627 rakwb eng Sckisel, Gail D. verfasserin aut Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. Results Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to $ CD62L^{low} $ (T effector/effector memory,$ T_{E/EM} $) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on $ T_{E/EM} $ cells was observed in patients undergoing systemic high-dose IL-2 therapy. Conclusions These data highlight PD-1 expressing and/or $ T_{E/EM} $ subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. Trial registration ClinicalTrials.gov NCT01416831. Registered August 12, 2011. Immunotherapy (dpeaa)DE-He213 Cancer (dpeaa)DE-He213 PD-1 (dpeaa)DE-He213 Bystander Activation (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 NKG2D (dpeaa)DE-He213 Mirsoian, Annie aut Minnar, Christine M. aut Crittenden, Marka aut Curti, Brendan aut Chen, Jane Q. aut Blazar, Bruce R. aut Borowsky, Alexander D. aut Monjazeb, Arta M. aut Murphy, William J. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 18. Apr. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:18 month:04 https://dx.doi.org/10.1186/s40425-017-0235-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 18 04 |
allfields_unstemmed |
10.1186/s40425-017-0235-4 doi (DE-627)SPR036435600 (SPR)s40425-017-0235-4-e DE-627 ger DE-627 rakwb eng Sckisel, Gail D. verfasserin aut Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. Results Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to $ CD62L^{low} $ (T effector/effector memory,$ T_{E/EM} $) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on $ T_{E/EM} $ cells was observed in patients undergoing systemic high-dose IL-2 therapy. Conclusions These data highlight PD-1 expressing and/or $ T_{E/EM} $ subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. Trial registration ClinicalTrials.gov NCT01416831. Registered August 12, 2011. Immunotherapy (dpeaa)DE-He213 Cancer (dpeaa)DE-He213 PD-1 (dpeaa)DE-He213 Bystander Activation (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 NKG2D (dpeaa)DE-He213 Mirsoian, Annie aut Minnar, Christine M. aut Crittenden, Marka aut Curti, Brendan aut Chen, Jane Q. aut Blazar, Bruce R. aut Borowsky, Alexander D. aut Monjazeb, Arta M. aut Murphy, William J. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 18. Apr. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:18 month:04 https://dx.doi.org/10.1186/s40425-017-0235-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 18 04 |
allfieldsGer |
10.1186/s40425-017-0235-4 doi (DE-627)SPR036435600 (SPR)s40425-017-0235-4-e DE-627 ger DE-627 rakwb eng Sckisel, Gail D. verfasserin aut Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. Results Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to $ CD62L^{low} $ (T effector/effector memory,$ T_{E/EM} $) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on $ T_{E/EM} $ cells was observed in patients undergoing systemic high-dose IL-2 therapy. Conclusions These data highlight PD-1 expressing and/or $ T_{E/EM} $ subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. Trial registration ClinicalTrials.gov NCT01416831. Registered August 12, 2011. Immunotherapy (dpeaa)DE-He213 Cancer (dpeaa)DE-He213 PD-1 (dpeaa)DE-He213 Bystander Activation (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 NKG2D (dpeaa)DE-He213 Mirsoian, Annie aut Minnar, Christine M. aut Crittenden, Marka aut Curti, Brendan aut Chen, Jane Q. aut Blazar, Bruce R. aut Borowsky, Alexander D. aut Monjazeb, Arta M. aut Murphy, William J. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 18. Apr. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:18 month:04 https://dx.doi.org/10.1186/s40425-017-0235-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 18 04 |
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10.1186/s40425-017-0235-4 doi (DE-627)SPR036435600 (SPR)s40425-017-0235-4-e DE-627 ger DE-627 rakwb eng Sckisel, Gail D. verfasserin aut Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. Results Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to $ CD62L^{low} $ (T effector/effector memory,$ T_{E/EM} $) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on $ T_{E/EM} $ cells was observed in patients undergoing systemic high-dose IL-2 therapy. Conclusions These data highlight PD-1 expressing and/or $ T_{E/EM} $ subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. Trial registration ClinicalTrials.gov NCT01416831. Registered August 12, 2011. Immunotherapy (dpeaa)DE-He213 Cancer (dpeaa)DE-He213 PD-1 (dpeaa)DE-He213 Bystander Activation (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 NKG2D (dpeaa)DE-He213 Mirsoian, Annie aut Minnar, Christine M. aut Crittenden, Marka aut Curti, Brendan aut Chen, Jane Q. aut Blazar, Bruce R. aut Borowsky, Alexander D. aut Monjazeb, Arta M. aut Murphy, William J. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 18. Apr. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:18 month:04 https://dx.doi.org/10.1186/s40425-017-0235-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 18 04 |
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differential phenotypes of memory cd4 and cd8 t cells in the spleen and peripheral tissues following immunostimulatory therapy |
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Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy |
abstract |
Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. Results Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to $ CD62L^{low} $ (T effector/effector memory,$ T_{E/EM} $) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on $ T_{E/EM} $ cells was observed in patients undergoing systemic high-dose IL-2 therapy. Conclusions These data highlight PD-1 expressing and/or $ T_{E/EM} $ subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. Trial registration ClinicalTrials.gov NCT01416831. Registered August 12, 2011. © The Author(s). 2017 |
abstractGer |
Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. Results Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to $ CD62L^{low} $ (T effector/effector memory,$ T_{E/EM} $) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on $ T_{E/EM} $ cells was observed in patients undergoing systemic high-dose IL-2 therapy. Conclusions These data highlight PD-1 expressing and/or $ T_{E/EM} $ subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. Trial registration ClinicalTrials.gov NCT01416831. Registered August 12, 2011. © The Author(s). 2017 |
abstract_unstemmed |
Background Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. Results Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to $ CD62L^{low} $ (T effector/effector memory,$ T_{E/EM} $) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on $ T_{E/EM} $ cells was observed in patients undergoing systemic high-dose IL-2 therapy. Conclusions These data highlight PD-1 expressing and/or $ T_{E/EM} $ subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. Trial registration ClinicalTrials.gov NCT01416831. Registered August 12, 2011. © The Author(s). 2017 |
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title_short |
Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy |
url |
https://dx.doi.org/10.1186/s40425-017-0235-4 |
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author2 |
Mirsoian, Annie Minnar, Christine M. Crittenden, Marka Curti, Brendan Chen, Jane Q. Blazar, Bruce R. Borowsky, Alexander D. Monjazeb, Arta M. Murphy, William J. |
author2Str |
Mirsoian, Annie Minnar, Christine M. Crittenden, Marka Curti, Brendan Chen, Jane Q. Blazar, Bruce R. Borowsky, Alexander D. Monjazeb, Arta M. Murphy, William J. |
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Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. Methods Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. 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