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CAML Is a p56Lck-Interacting Protein that Is Required for Thymocyte Development

2005; Cell Press; Volume: 23; Issue: 2 Linguagem: Inglês

10.1016/j.immuni.2005.06.006

1097-4180

David Tran, Contessa E. Edgar, Karin L. Heckman, Shari L. Sutor, Catherine J. Huntoon, Jan van Deursen, David L. McKean, Richard J. Bram,

Galectins and Cancer Biology

Calcium modulating cyclophilin ligand (CAML) is a ubiquitously expressed protein implicated in T cell signaling, although its mechanism and physiologic role in the immune system are unknown. We show here that CAML is essential for peripheral T cell development. Inactivation of CAML in mouse thymocytes lowered the numbers of double-positive and single-positive thymocytes, concomitant with reduced positive and enhanced negative selection. We found that CAML interacts with p56Lck and appears to regulate subcellular localization of the kinase in both resting and T cell receptor (TCR)-stimulated cells. CAML-deficient cells displayed enhanced p56lck and ZAP-70 phosphorylation and increased IL2 production and cell death after TCR stimulation, suggesting that CAML may act as a negative regulator of p56lck. Our data establish a novel role for CAML as an essential mediator of T cell survival during thymopoiesis and indicate that its loss deregulates p56Lck signaling.