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Calcium-Modulating Cyclophilin Ligand Is Essential for the Survival of Activated T Cells and for Adaptive Immunity

2015; American Association of Immunologists; Volume: 195; Issue: 12 Linguagem: Inglês

10.4049/jimmunol.1500308

1550-6606

Siaw-Li Chan, Lonn D. Lindquist, Michael J. Hansen, Megan A. Girtman, Larry R. Pease, Richard J. Bram,

Galectins and Cancer Biology

Abstract Calcium-modulating cyclophilin ligand (CAML) is an endoplasmic reticulum resident protein that is widely expressed. Although it has been demonstrated to participate in the tail-anchored protein insertion pathway, its physiological role in the mature immune system is unknown. In this work, we show that mature, peripheral T cells require CAML for survival specifically following TCR-induced activation. In this study, we examined mature T cells from spleen and lymph nodes of tamoxifen-inducible CAML knockout mice (tCAML−/−). Whereas CAML-deficient T cells were able to express the early activation markers CD25 and CD69, and produce IL-2 normally upon stimulation, deficient cells proliferated less and died. Cells did not require CAML for entry into the S phase of the cell cycle, thus implicating its survival function at a relatively late step in the T cell activation sequence. In addition, CAML was required for homeostatic proliferation and for Ag-dependent cell killing in vivo. These results demonstrate that CAML critically supports T cell survival and cell division downstream of T cell activation.