Biomedical research institute
     
    You are here: Home / Departments / Infection, Immunity and Inflammation / Team B. Lucas / Physiology of γ/δ T cells

    Physiology of γ/δ T cells

    •  

     

    Objective


    γ/δ T cells are a well-conserved T-cell population throughout evolution and across species. Indeed, in every vertebrate in which T-cell ontogeny has been examined, γ/δ T cells appear to be the first T cells to develop. g/d T cells are unique and distinct from other lymphocyte subsets, in that they combine adaptive features with rapid, innate-like responses that allow them to play an important role in all phases of an immune response.

    However, the paucity of the present knowledge on γ/δ TCR ligands compromises the in deep characterization of their physiological functions in the periphery. It is thus crucial to identify markers highlighting the existence of distinct phenotypic and functional γ/δ T-cell subsets.

    Interestingly, we recently observed that 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 naïve and memory CD8+α/β T cells, we show that Ly-6C- or + CD44lo and Ly-6C+ CD44hi γ/δ T cells greatly resemble to, and behave like, their CD8+α/β T-cell counterparts. More precisely, peripheral CD27+ γ/δ T cells, commonly considered as an homogeneous T-cell compartment, actually share many common features with adaptive α/β T cells as both lineages include “naïve-like” and “memory-like” lymphocytes with distinct phenotypic, functional and homeostatic characteristics (Lombes et al. manuscript submitted).

     

    Presently, we now plan to extend our work by:

    1. Defining the meaning of Ly-6C expression or non-expression on CD44lo “naïve-like” γ/δ T cells. The main question will be: does Ly-6C expression reveal a functional dichotomy within the  “naïve-like” γ/δ T cell compartment?
    2. Characterizing the localization and behavior of γ/δ T cell subsets within lymph nodes.
    3. Studying, in vivo, the differentiation capacities into effector cells (such as TH1-like, TH17-like or iTreg-like) of γ/δ T cells. Indeed, in vitro polarization assays have revealed the capacity of “naïve like” γ/δ T cells to differentiate into a broad variety of effector cells including IFNγ+, IL-17+ or Foxp3 expressing γ/δ T cells. We now plan to examine γ/δ T cell plasticity in tumour context.

     

    Clarifying these issues will participate in our better understanding of the function of γ/δ T cells.


    Principales publications

     

    • Lombes A, Durand A, Charvet C, Rivière M, Bonilla N, Auffray C, Lucas B, Martin B. Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts. J Immunol. 2015 195(12):1449-58.
    • Delpoux, A., Yakonowsky, P., Durand, A., Charvet, C., Valente, M., Pommier, A., Bonilla, N., Martin, B., Auffray, C.*, Lucas, B.* TCR Signaling Events Are Required for Maintaining CD4 Regulatory T Cell Numbers and Suppressive Capacities in the Periphery J Immunol 2014; 193(12):5914-23
    • Martin, B.*, Auffray, C.*, Delpoux, A., Pommier, A., Durand, A., Charvet, C., Yakonowsky, P., de Boysson, H., Bonilla, N., Audemard, A., Sparwasser, T., Salomon, B. L., Malissen, B., Lucas, B. Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells Nat Commun 2013; 4:2209.
    • Pommier, A., Audemard, A., Durand, A., Lengagne, R., Delpoux, A., Martin, B., Douguet, L., Le Campion, A., Kato, M., Avril, M. F., Auffray, C., Lucas, B.*, Prevost-Blondel, A.* Inflammatory monocytes are potent antitumor effectors controlled by regulatory CD4+ T cells Proc Natl Acad Sci U S A 2013; 110(32):13085-90.
    • Le Campion, A., Pommier, A., Delpoux, A., Stouvenel, L., Auffray, C., Martin, B.*, Lucas, B.* IL-2 and IL-7 Determine the Homeostatic Balance between the Regulatory and Conventional CD4+ T Cell Compartments during Peripheral T Cell Reconstitution J Immunol 2012; 189(7):3339-46.
    • K. Hirota, B. Martin, M. Veldhoen. 2010. Development, regulation and functional capacities of Th17 cells. Seminars in Immunopathology,  32(1):3-16.
    • Le Campion, A., Gagnerault, M. C., Auffray, C., Becourt, C., Poitrasson-Riviere, M., Lallemand, E., Bienvenu, B., Martin, B., Lepault, F., Lucas, B. Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease development Blood 2009; 114(9):1784-93
    • B. Martin, K. Hirota, D. J. Cua, B. Stockinger and M. Veldhoen. 2009. IL-17 Producing γδ T cells selectively expand in response to pathogen products and environmental signals. Immunity, 31(2) : 321-30.
    • Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, Martin B, Wilhelm C, Stockinger B. 2008. Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nature Immunol. 12:1341-6.
    • B. Stockinger, M. Veldhoen, B. Martin. 2007. Th17 T cells : Linking innate and adaptive immunity. Seminars in Immunology 2007.10.008.



    Departments