Biomedical research institute
     
    You are here: Home / Departments / Infection, Immunity and Inflammation / Team B. Lucas

    Team : Regulation of T Cell effector functions: from basic research to cancer

    •  

    Team leader 

     

    We conduct an exploratory type of basic research that aims at a better understanding of the contribution of steady state interactions between T cells and their environment in both the maintenance of immune tolerance and the ability of the immune system to mount efficient reponses in various pathologic conditions. In particular, our projects raise important points regarding the regulation of T-cell responses to self antigens in the steady state.

    Objectives

     

    In the absence of foreign antigen, peripheral naive T cells continuously recirculate between different lymphoid organs, in which they interact frequently and shortly with self. We and others have shown that such interactions are required for the long-term survival of naïve T cells. In addition, these TCR/MHC interactions and the resulting associated signaling increase quantitatively T-cell responsiveness towards foreign antigens and influence their function and/or differentiation into effector or memory cells in response to stimulation. Our project is based on our recent data showing that peripheral ab and  gd T cells can be subdivided into various subsets according to Ly-6C expression. Interestingly, in CD4 ab T cells, Ly-6C expression inversely correlates with the ability of these cells to interact with self, defining Ly-6C as a new sensor of T cell self-reactivity.

    In parallel, we are exploring the regulation of T-cell self-reactivity in the context of cancer. Indeed, T cells specific for melanoma recognize differentiation antigens shared by normal melanocytes and melanoma-associated vitiligo is the best example of a linkage between anti-tumor immunity and autoimmunity. Our aim is to better characterize T cell functions in a mouse model of spontaneous metastatic melanoma associated with a vitiligo in 40% of cases (RET mice). In RET mice, myeloid cells massively infiltrate primary and metastatic tumors and inhibit T cells through various mechanisms. We are focusing our interest on inducible nitric oxyde synthase (NOS2) and IL4 induced gene 1 (IL4I1), both essentially expressed by myeloid cells, that may affect T-cell effector properties.

    The main topics developped in our team are the following:

    - Self-mediated shaping of naïve CD4 T-cell effector fate (C. Auffray)

    - Physiology of regulatory Foxp3+ CD4 T cells (B. Lucas)

    - Physiology of gd T cells (B. Martin)

     

    Main publications (2011-2017)

     

    • Taleb K, Auffray C, Villefroy P, Pereira A, Hosmalin A, Gaudry M, Le Bon A. 2016. Chronic Type I IFN Is Sufficient To Promote Immunosuppression through Accumulation of Myeloid-Derived Suppressor Cells. J Immunol.198:1156-1163
    • Llitjos JF, Auffray C, Alby-Laurent F, Rousseau C, Merdji H, Bonilla N, Toubiana J, Belaïdouni N, Mira JP, Lucas B, Chiche JD, Pène F. 2017. Sepsis-induced expansion of granulocytic myeloid-derived suppressor cells promotes tumour growth through Toll-like receptor 4. J Pathol. 239:473-83.
    • Lombes A, Durand A, Charvet C, Rivière M, Bonilla N, Auffray C, Lucas B*, Martin B*. 2015. Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts. J Immunol. 195:1449-58.
    • Lainé A, Martin B, Luka M, Mir L, Auffray C, Lucas B, Bismuth G, Charvet C. 2015. Foxo1 Is a T Cell-Intrinsic Inhibitor of the RORγt-Th17 Program. J Immunol. 195:1791-803.
    • Delpoux, A, Yakonowsky, P, Durand, A, Charvet, C, Valente, M, Pommier, A, Bonilla, N, Martin, B, Auffray, C*, Lucas, B*. 2014. TCR Signaling Events Are Required for Maintaining CD4 Regulatory T Cell Numbers and Suppressive Capacities in the Periphery J Immunol. 193:5914-23.
    • Martin B*, Auffray C*, Delpoux A, Pommier A, Charvet C, Yakonowsky P, de Boysson H, Audemard A, Malissen B, Lucas B. 2013. Differentiation into induced regulatory T cells: all naïve CD4 T cells are not created equal. Nat Commun. 4:2209.
    • Pommier A, Delpoux A, Audemard A, Martin B, Douguet L, Lengagne R, Kato M, Avril MF, Auffray C, Lucas B*, Prévost-Blondel A*. 2013.Ly6Chigh monocytes are potent anti-tumor effectors controlled by regulatory CD4 T cells. PNAS. 110:13085-90.
    • Le Campion A, A Pommier, A Delpoux, L Stouvenel, C Auffray, B Martin* and B Lucas*. 2012. 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. 189:3339-46.
    • Delpoux, A, M Poitrasson-Rivière, A Le Campion, A Pommier, P Yakonowsky, S Jacques, F Letourneur, C Randriamampita, B Lucas*, and C Auffray*. 2012. Foxp3-independent loss of regulatory CD4+ T-cell suppressive capacities induced by self-deprivation. Eur J Immunol 42:1237-49.
    • Lengagne, R, A Pommier, J Caron, L Douguet, M Garcette, M Kato, MF Avril, JP Abastado, N Bercovici, B Lucas, and A Prevost-Blondel. 2011. T cells contribute to tumor progression by favoring pro-tumoral properties of intra-tumoral myeloid cells in a mouse model for spontaneous melanoma. PLoS One 6:e20235.

    * Equal contribution to the paper

     

    Team's news

    • The team has been awarded the “FRM team” label (from 10/2014 to 10/2017)
    • Bruno Lucas is scientific deputy director of the Institute for biological Sciences of the CNRS since 2012.
    • Cédric Auffray has been awarded by the French Academy of Sciences in 2008