title: Calcium-Modulating Cyclophilin Ligand Is Essential for the Survival of Activated T Cells and for Adaptive Immunity.
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.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905; and.
authors.forename: Siaw-Li
authors.identifier: http://orcid.org/0000-0001-9595-9430
authors.initials: SL
authors.lastname: Chan
authors.affiliation: Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905.
authors.forename: Lonn D
authors.initials: LD
authors.lastname: Lindquist
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905; and.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hansen
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905; and.
authors.forename: Megan A
authors.identifier: http://orcid.org/0000-0002-9880-8045
authors.initials: MA
authors.lastname: Girtman
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905; and.
authors.forename: Larry R
authors.initials: LR
authors.lastname: Pease
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905; and Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905 bramr@mayo.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bram
mesh_terms: D056704:Adaptive Immunity; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D021983:Cyclophilins / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490314:Caml protein, mouse; D008024:Ligands; D021983:Cyclophilins; D002118:Calcium