Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses

Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authen...
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Autor*in:	Takeshi Kawabe [verfasserIn] Thomas Ciucci [verfasserIn] Kwang Soon Kim [verfasserIn] Shunichi Tayama [verfasserIn] Akihisa Kawajiri [verfasserIn] Takumi Suzuki [verfasserIn] Riou Tanaka [verfasserIn] Naoto Ishii [verfasserIn] Dragana Jankovic [verfasserIn] Jinfang Zhu [verfasserIn] Jonathan Sprent [verfasserIn] Rémy Bosselut [verfasserIn] Alan Sher [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	CD4+ T lymphocytes memory homeostasis innate immunity phenotypic analysis

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2022.870542

Katalog-ID:	DOAJ042110467

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allfields	10.3389/fimmu.2022.870542 doi (DE-627)DOAJ042110467 (DE-599)DOAJd66f6ac930a24af8947edeb2266a5f97 DE-627 ger DE-627 rakwb eng RC581-607 Takeshi Kawabe verfasserin aut Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells. CD4+ T lymphocytes memory homeostasis innate immunity phenotypic analysis Immunologic diseases. Allergy Takeshi Kawabe verfasserin aut Thomas Ciucci verfasserin aut Thomas Ciucci verfasserin aut Kwang Soon Kim verfasserin aut Shunichi Tayama verfasserin aut Akihisa Kawajiri verfasserin aut Takumi Suzuki verfasserin aut Riou Tanaka verfasserin aut Naoto Ishii verfasserin aut Dragana Jankovic verfasserin aut Jinfang Zhu verfasserin aut Jonathan Sprent verfasserin aut Jonathan Sprent verfasserin aut Rémy Bosselut verfasserin aut Alan Sher verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.870542 kostenfrei https://doaj.org/article/d66f6ac930a24af8947edeb2266a5f97 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.870542/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
spelling	10.3389/fimmu.2022.870542 doi (DE-627)DOAJ042110467 (DE-599)DOAJd66f6ac930a24af8947edeb2266a5f97 DE-627 ger DE-627 rakwb eng RC581-607 Takeshi Kawabe verfasserin aut Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells. CD4+ T lymphocytes memory homeostasis innate immunity phenotypic analysis Immunologic diseases. Allergy Takeshi Kawabe verfasserin aut Thomas Ciucci verfasserin aut Thomas Ciucci verfasserin aut Kwang Soon Kim verfasserin aut Shunichi Tayama verfasserin aut Akihisa Kawajiri verfasserin aut Takumi Suzuki verfasserin aut Riou Tanaka verfasserin aut Naoto Ishii verfasserin aut Dragana Jankovic verfasserin aut Jinfang Zhu verfasserin aut Jonathan Sprent verfasserin aut Jonathan Sprent verfasserin aut Rémy Bosselut verfasserin aut Alan Sher verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.870542 kostenfrei https://doaj.org/article/d66f6ac930a24af8947edeb2266a5f97 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.870542/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
allfields_unstemmed	10.3389/fimmu.2022.870542 doi (DE-627)DOAJ042110467 (DE-599)DOAJd66f6ac930a24af8947edeb2266a5f97 DE-627 ger DE-627 rakwb eng RC581-607 Takeshi Kawabe verfasserin aut Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells. CD4+ T lymphocytes memory homeostasis innate immunity phenotypic analysis Immunologic diseases. Allergy Takeshi Kawabe verfasserin aut Thomas Ciucci verfasserin aut Thomas Ciucci verfasserin aut Kwang Soon Kim verfasserin aut Shunichi Tayama verfasserin aut Akihisa Kawajiri verfasserin aut Takumi Suzuki verfasserin aut Riou Tanaka verfasserin aut Naoto Ishii verfasserin aut Dragana Jankovic verfasserin aut Jinfang Zhu verfasserin aut Jonathan Sprent verfasserin aut Jonathan Sprent verfasserin aut Rémy Bosselut verfasserin aut Alan Sher verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.870542 kostenfrei https://doaj.org/article/d66f6ac930a24af8947edeb2266a5f97 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.870542/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
allfieldsGer	10.3389/fimmu.2022.870542 doi (DE-627)DOAJ042110467 (DE-599)DOAJd66f6ac930a24af8947edeb2266a5f97 DE-627 ger DE-627 rakwb eng RC581-607 Takeshi Kawabe verfasserin aut Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells. CD4+ T lymphocytes memory homeostasis innate immunity phenotypic analysis Immunologic diseases. Allergy Takeshi Kawabe verfasserin aut Thomas Ciucci verfasserin aut Thomas Ciucci verfasserin aut Kwang Soon Kim verfasserin aut Shunichi Tayama verfasserin aut Akihisa Kawajiri verfasserin aut Takumi Suzuki verfasserin aut Riou Tanaka verfasserin aut Naoto Ishii verfasserin aut Dragana Jankovic verfasserin aut Jinfang Zhu verfasserin aut Jonathan Sprent verfasserin aut Jonathan Sprent verfasserin aut Rémy Bosselut verfasserin aut Alan Sher verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.870542 kostenfrei https://doaj.org/article/d66f6ac930a24af8947edeb2266a5f97 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.870542/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
allfieldsSound	10.3389/fimmu.2022.870542 doi (DE-627)DOAJ042110467 (DE-599)DOAJd66f6ac930a24af8947edeb2266a5f97 DE-627 ger DE-627 rakwb eng RC581-607 Takeshi Kawabe verfasserin aut Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells. CD4+ T lymphocytes memory homeostasis innate immunity phenotypic analysis Immunologic diseases. Allergy Takeshi Kawabe verfasserin aut Thomas Ciucci verfasserin aut Thomas Ciucci verfasserin aut Kwang Soon Kim verfasserin aut Shunichi Tayama verfasserin aut Akihisa Kawajiri verfasserin aut Takumi Suzuki verfasserin aut Riou Tanaka verfasserin aut Naoto Ishii verfasserin aut Dragana Jankovic verfasserin aut Jinfang Zhu verfasserin aut Jonathan Sprent verfasserin aut Jonathan Sprent verfasserin aut Rémy Bosselut verfasserin aut Alan Sher verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.870542 kostenfrei https://doaj.org/article/d66f6ac930a24af8947edeb2266a5f97 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.870542/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
language	English
source	In Frontiers in Immunology 13(2022) volume:13 year:2022
sourceStr	In Frontiers in Immunology 13(2022) volume:13 year:2022
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	CD4+ T lymphocytes memory homeostasis innate immunity phenotypic analysis Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Takeshi Kawabe @@aut@@ Thomas Ciucci @@aut@@ Kwang Soon Kim @@aut@@ Shunichi Tayama @@aut@@ Akihisa Kawajiri @@aut@@ Takumi Suzuki @@aut@@ Riou Tanaka @@aut@@ Naoto Ishii @@aut@@ Dragana Jankovic @@aut@@ Jinfang Zhu @@aut@@ Jonathan Sprent @@aut@@ Rémy Bosselut @@aut@@ Alan Sher @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ042110467
language_de	englisch
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callnumber-first	R - Medicine
author	Takeshi Kawabe
spellingShingle	Takeshi Kawabe misc RC581-607 misc CD4+ T lymphocytes misc memory misc homeostasis misc innate immunity misc phenotypic analysis misc Immunologic diseases. Allergy Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses
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topic_title	RC581-607 Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses CD4+ T lymphocytes memory homeostasis innate immunity phenotypic analysis
topic	misc RC581-607 misc CD4+ T lymphocytes misc memory misc homeostasis misc innate immunity misc phenotypic analysis misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc CD4+ T lymphocytes misc memory misc homeostasis misc innate immunity misc phenotypic analysis misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc CD4+ T lymphocytes misc memory misc homeostasis misc innate immunity misc phenotypic analysis misc Immunologic diseases. Allergy
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title	Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses
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title_full	Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses
author_sort	Takeshi Kawabe
journal	Frontiers in Immunology
journalStr	Frontiers in Immunology
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author_browse	Takeshi Kawabe Thomas Ciucci Kwang Soon Kim Shunichi Tayama Akihisa Kawajiri Takumi Suzuki Riou Tanaka Naoto Ishii Dragana Jankovic Jinfang Zhu Jonathan Sprent Rémy Bosselut Alan Sher
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author-letter	Takeshi Kawabe
doi_str_mv	10.3389/fimmu.2022.870542
author2-role	verfasserin
title_sort	redefining the foreign antigen and self-driven memory cd4+ t-cell compartments via transcriptomic, phenotypic, and functional analyses
callnumber	RC581-607
title_auth	Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses
abstract	Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells.
abstractGer	Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells.
abstract_unstemmed	Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific “authentic” memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells.
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title_short	Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses
url	https://doi.org/10.3389/fimmu.2022.870542 https://doaj.org/article/d66f6ac930a24af8947edeb2266a5f97 https://www.frontiersin.org/articles/10.3389/fimmu.2022.870542/full https://doaj.org/toc/1664-3224
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author2	Takeshi Kawabe Thomas Ciucci Kwang Soon Kim Shunichi Tayama Akihisa Kawajiri Takumi Suzuki Riou Tanaka Naoto Ishii Dragana Jankovic Jinfang Zhu Jonathan Sprent Rémy Bosselut Alan Sher
author2Str	Takeshi Kawabe Thomas Ciucci Kwang Soon Kim Shunichi Tayama Akihisa Kawajiri Takumi Suzuki Riou Tanaka Naoto Ishii Dragana Jankovic Jinfang Zhu Jonathan Sprent Rémy Bosselut Alan Sher
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up_date	2024-07-03T23:40:48.091Z
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