Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells

Martin, Bruno; Auffray, Cédric; Delpoux, Arnaud; Pommier, Arnaud; Durand, Aurélie; Charvet, Céline; Yakonowsky, Philippe; Boysson, Hubert de; Bonilla, Nelly; Audemard, A.; Sparwasser, Tim; Salomon, Benoı̂t L.; Malissen, Bernard; Lucas, Bruno

doi:10.1038/ncomms3209

Cited by 63 publications

(86 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…combined with increasing TGF-b concentrations (37). In this assay, the percentage of iTh17 in the control condition reached a maximal peak at low TGF-b concentrations (0.031-0.25 ng/ml) when combined with IL-6, and gradually decreased with higher doses of TGF-b ( Fig.…”

Section: Foxo1 Deficiency In T Cells Leads To An Increase Of Th17 Celmentioning

confidence: 78%

Foxo1 Is a T Cell–Intrinsic Inhibitor of the RORγt-Th17 Program

Laine

Martin

Luka

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

An uncontrolled exaggerated Th17 response can drive the onset of autoimmune and inflammatory diseases. In this study, we show that, in T cells, Foxo1 is a negative regulator of the Th17 program. Using mixed bone marrow chimeras and Foxo1-deficient mice, we demonstrate that this control is effective in vivo, as well as in vitro during differentiation assays of naive T cells with specific inhibitor of Foxo1 or inhibitors of the PI3K/Akt pathway acting upstream of Foxo1. Consistently, expressing this transcription factor in T cells strongly decreases Th17 generation in vitro as well as transcription of both IL-17A and IL-23R RORγt-target genes. Finally, at the molecular level, we demonstrate that Foxo1 forms a complex with RORγt via its DNA binding domain to inhibit RORγt activity. We conclude that Foxo1 is a direct antagonist of the RORγt-Th17 program acting in a T cell–intrinsic manner.

show abstract

Section: Foxo1 Deficiency In T Cells Leads To An Increase Of Th17 Celmentioning

confidence: 78%

Foxo1 Is a T Cell–Intrinsic Inhibitor of the RORγt-Th17 Program

Laine

Martin

Luka

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Likewise, we do not know whether private peptides on cTECs are equally important for CD4 + and CD8 + T cell repertoire selection. This question is all the more interesting since high tonic self-responders among naïve CD4 + T cells seem inherently more prone to undergo peripheral conversion into induced FOXP3 + T Reg cells 82 .…”

Section: Perspectivesmentioning

confidence: 99%

Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see)

et al. 2014

View full text Add to dashboard Cite

The fate of developing T cells is specified by interactions of their antigen receptor with self-peptide/MHC complexes displayed by thymic antigen presenting cells (APCs). Various thymic APCs subsets are strategically positioned in particular thymic microenvironments and orchestrate the selection of a functional and self-tolerant T cell repertoire. Here, we will review the different strategies that these APCs employ to sample and process self-antigens and thereby generate partly unique, ‘idiosyncratic’ peptide/MHC ligandomes. We will discuss how the particular composition of these APC-subset-specific peptide/MHC ligandomes not only shapes the T cell repertoire in the thymus, but may also indelibly imprint the behavior of mature T cells in the periphery.

show abstract

“…We recently showed that peripheral Tregs and naive CD4 + a/b T cells can be subdivided into two subsets according to Ly-6C expression and that these newly defined subsets were functionally not equal (34,41). In this study, we noticed that, in both the a/b CD8 + T cell and g/d T cell compartments, CD44 lo Ly-6C + cells exhibit a greater ability to produce IFN-g than their Ly-6C 2 cell counterparts ex vivo.…”

Section: Cd44mentioning

confidence: 99%

“…In this study, we noticed that, in both the a/b CD8 + T cell and g/d T cell compartments, CD44 lo Ly-6C + cells exhibit a greater ability to produce IFN-g than their Ly-6C 2 cell counterparts ex vivo. One can thus wonder whether, as observed for naive and regulatory CD4 + a/b T cells (34,41), Ly-6C expression or nonexpression within the naive a/b CD8 + T cell and the naive-like g/d T cell compartments could reflect distinct functional features.…”

Section: Cd44mentioning

confidence: 99%

Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts

Lombès

Durand

Charvet

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

To better apprehend γ/δ T cell biological functions in the periphery, it appears crucial to identify markers highlighting the existence of distinct phenotypic and functional γ/δ T cell subsets. Interestingly, the expression of CD44 and Ly-6C subdivides murine peripheral γ/δ T cells into several subsets, with Ly-6C− CD44hi γ/δ T cells corresponding to the IL-17–producing CD27− γ/δ T cell subset exhibiting innate-like features. By comparing the other subsets to naive and memory CD8+ α/β T cells, in this study, we show that Ly-6C− or + CD44lo and Ly-6C+CD44hi γ/δ T cells greatly resemble, and behave like, their CD8+ α/β T cell counterparts. First, like memory CD8+ α/β T cells, Ly-6C+CD44hi γ/δ T cells are sparse in the thymus but largely increased in proportion in tissues. Second, similarly to naive CD8 α/β T cells, CD44lo γ/δ T cells are poorly cycling in vivo in the steady state, and their proportion declines with age in secondary lymphoid organs. Third, CD44lo γ/δ T cells undergo spontaneous proliferation and convert to a memory-like Ly-6C+CD44hi phenotype in response to lymphopenia. Finally, CD44lo γ/δ T cells have an intrinsic high plasticity as, upon appropriate stimulation, they are capable of differentiating nonetheless into Th17-like and Th1-like cells but also into fully functional Foxp3+ induced regulatory T cell–like γ/δ T cells. Thus, peripheral CD27+ γ/δ T cells, commonly considered as a functionally related T cell compartment, actually share many common features with adaptive α/β T cells, as both lineages include naive-like and memory-like lymphocytes with distinct phenotypic, functional, and homeostatic characteristics.

show abstract

Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells

Cited by 63 publications

References 54 publications

Foxo1 Is a T Cell–Intrinsic Inhibitor of the RORγt-Th17 Program

Foxo1 Is a T Cell–Intrinsic Inhibitor of the RORγt-Th17 Program

Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see)

Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts

Contact Info

Product

Resources

About