Journal ArticleDOI
Follicular Helper CD4 T Cells (TFH)
TLDR
This review discusses recent progress and areas of uncertainty or disagreement in the literature, and debates the developmental relationship between T(FH) cells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).Abstract:
T cell help to B cells is a fundamental aspect of adaptive immunity and the generation of immunological memory. Follicular helper CD4 T (T(FH)) cells are the specialized providers of B cell help. T(FH) cells depend on expression of the master regulator transcription factor Bcl6. Distinguishing features of T(FH) cells are the expression of CXCR5, PD-1, SAP (SH2D1A), IL-21, and ICOS, among other molecules, and the absence of Blimp-1 (prdm1). T(FH) cells are important for the formation of germinal centers. Once germinal centers are formed, T(FH) cells are needed to maintain them and to regulate germinal center B cell differentiation into plasma cells and memory B cells. This review covers T(FH) differentiation, T(FH) functions, and human T(FH) cells, discussing recent progress and areas of uncertainty or disagreement in the literature, and it debates the developmental relationship between T(FH) cells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).read more
Citations
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Journal ArticleDOI
T follicular helper cell differentiation, function, and roles in disease
TL;DR: There has been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs.
Journal ArticleDOI
The role of interleukin-2 during homeostasis and activation of the immune system.
TL;DR: Interleukin-2 signals influence various lymphocyte subsets during differentiation, immune responses and homeostasis and can amplify CD8+ T cell responses or induce the expansion of the TReg cell population, thus favouring either immune stimulation or suppression.
Journal ArticleDOI
Defining CD8 + T cells that provide the proliferative burst after PD-1 therapy
Se Jin Im,Masao Hashimoto,Michael Y. Gerner,Michael Y. Gerner,Junghwa Lee,Haydn T. Kissick,Matheus Carvalho Bürger,Qiang Shan,J. Scott Hale,Judong Lee,Tahseen H. Nasti,Arlene H. Sharpe,Arlene H. Sharpe,Gordon J. Freeman,Ronald N. Germain,Helder I. Nakaya,Hai-Hui Xue,Rafi Ahmed +17 more
TL;DR: A population of virus-specific CD8+ T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus is identified and its findings provide a better understanding of T-cell exhaustion and have implications in the optimization of PD- 1-directed immunotherapy in chronic infections and cancer.
Journal ArticleDOI
A Validated Regulatory Network for Th17 Cell Specification
Maria Ciofani,Aviv Madar,Aviv Madar,Carolina Galan,MacLean Sellars,Kieran Mace,Florencia Pauli,Ashish Agarwal,Wendy Huang,Christopher N. Parkurst,Michael Muratet,Kim M. Newberry,Sarah Meadows,Alex Greenfield,Yi Yang,Preti Jain,Francis K. Kirigin,Carmen Birchmeier,Erwin F. Wagner,Kenneth M. Murphy,Kenneth M. Murphy,Richard M. Myers,Richard Bonneau,Richard Bonneau,Dan R. Littman,Dan R. Littman +25 more
TL;DR: It is found that cooperatively bound BATF and IRF4 contribute to initial chromatin accessibility and, with STAT3, initiate a transcriptional program that is then globally tuned by the lineage-specifying TF RORγt, which plays a focal deterministic role at key loci.
Journal ArticleDOI
ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6.
Youn Soo Choi,Robin Kageyama,Danelle Eto,Tania C. Escobar,Robert J. Johnston,Robert J. Johnston,Laurel A. Monticelli,Christopher Lao,Shane Crotty,Shane Crotty +9 more
TL;DR: It is determined that Tfh cell development initiates immediately during dendritic cell (DC) priming in vivo, and it is demonstrated that inducible costimulator (ICOS) provides a critical early signal to induce the transcription factor Bcl6, and Bcl 6 then induces CXCR5, the canonical feature of T fh cells.
References
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Journal ArticleDOI
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PD-1 and its ligands in tolerance and immunity
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Journal ArticleDOI
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TL;DR: In this article, the authors analyzed genes expressed in functionally impaired virus-specific CD8 T cells present in mice chronically infected with lymphocytic choriomeningitis virus (LCMV), and compared these with the gene profile of functional memory CD8T cells.
Journal ArticleDOI
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Peter C. Heinrich,Iris Behrmann,Serge Haan,Heike M. Hermanns,Gerhard Müller-Newen,Fred Schaper +5 more
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Journal Article
Restoring function in exhausted CD8 T cells during chronic viral infection
TL;DR: It is found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the ‘helpless’ CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load.
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