The anti-apoptotic Bcl-2 family member Mcl-1 promotes T lymphocyte survival at multiple stages

I Dzhagalov, A Dunkle, YW He - The Journal of Immunology, 2008 - journals.aai.org
The Journal of Immunology, 2008journals.aai.org
T lymphocyte development and function are tightly regulated by the intrinsic death pathway
through members of the Bcl-2 family. Genetic studies have demonstrated that the Bcl-2
family member Mcl-1 is an important anti-apoptotic protein in the development of multiple
cell types including T lymphocytes. However, the expression pattern and anti-apoptotic roles
of Mcl-1 in T lymphocytes at different developmental stages remain to be fully determined. In
this study, we examined the expression pattern of Mcl-1 in different populations of T cells at …
Abstract
T lymphocyte development and function are tightly regulated by the intrinsic death pathway through members of the Bcl-2 family. Genetic studies have demonstrated that the Bcl-2 family member Mcl-1 is an important anti-apoptotic protein in the development of multiple cell types including T lymphocytes. However, the expression pattern and anti-apoptotic roles of Mcl-1 in T lymphocytes at different developmental stages remain to be fully determined. In this study, we examined the expression pattern of Mcl-1 in different populations of T cells at the single-cell level and found that Mcl-1 protein is constitutively expressed in all T cell populations and up-regulated upon TCR stimulation. We then investigated the role of Mcl-1 in the survival of these different populations by conditionally deleting Mcl-1 at various T cell stages. Our results show that Mcl-1 is required for the survival of double-negative and single-positive thymocytes as well as naive and activated T cells. Furthermore, we demonstrate that Mcl-1 functions together with Bcl-x L to promote double-positive thymocyte survival. Thus, Mcl-1 is a critical anti-apoptotic factor for the survival of T cells at multiple stages in vivo.
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