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The Bcl-2-associated X protein (Bax) and Bcl-2-antagonist/killer (Bak) are essential regulators of lymphocyte apoptosis, but whether they play a role in viable T cell function remains unclear. Here, we report that T cells lacking both Bax and Bak display defects in antigen-specific proliferation because of Ca 2+ -signaling defects. Bax −/− , Bak −/− T cells displayed defective...
For initiation of an immune response, resting T cells must reprogram their metabolism. Continuing the “From the Field” series (see Editorial [2007] 26, 131), Jones and Thompson draw attention to the importance of metabolism during T cell activation and consider how this process is regulated by receptor-mediated signal transduction.
Lymphocyte activation initiates a program of cell growth, proliferation, and differentiation that increases metabolic demand. Although T cells increase glucose uptake and glycolysis during an immune response, the signaling pathways that regulate these increases remain largely unknown. Here we show that CD28 costimulation, acting through phosphatidylinositol 3'-kinase (PI3K) and Akt, is required for...
CD28 and CTLA-4 are related members of a family of T lymphocyte cell surface receptors that function to regulate T cell activation. We have found that the cytoplasmic domains of both CTLA-4 and CD28 can associate with members of the PP2A family of serine/threonine phosphatases. The association of PP2A with CD28 was negatively regulated by tyrosine phosphorylation of the CD28 cytoplasmic domain. Inhibition...
CD28 ligation delivers a costimulatory signal important in T cell activation. This study demonstrates that the disruption of the CD28/B7 pathway early in the nonobese diabetic mouse strain, using CD28 -/- and CTLA4lg transgenic mice, promoted the development and progression of spontaneous autoimmune diabetes. Functional analyses of T cells isolated from CD28 deficient mice demonstrated...
T cell activation through the TCR can result in either cell proliferation or cell death. The role of costimulatory receptors i n regulating T cell survival has not been defined. Here, we present data demonstrating that CD28 costimulation enhances the in vitro survival of activated T cells. One mechanism for this enhancement is the ability of CD28 costimulation to augment the production of IL-2, which...
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