Activation of p38 mitogen-activated protein kinase in vivo selectively induces apoptosis of CD8(+) but not CD4(+) T cells

CD4(+) and CD8(+) T cells play specific roles during an immune response. Di fferent molecular mechanisms could regulate the proliferation, death, and e ffector functions of these two subsets of T cells. The p38 mitogen-activate d protein (MAP) kinase pathway is induced by cytokines and environmental st ress and has been associated with cell death and cytokine expression. Here me report that activation of the p38 MAP kinase pathway in vivo causes a se lective loss of CD8(+) T cells due to the induction of apoptosis. In contra st, activation of p38 MAP kinase does not induce CD4(+) T-cell death. The a poptosis of CD8(+) T cells is associated with decreased expression of the a ntiapoptotic protein Bcl-2. Regulation of the p38 MAP kinase pathway in T c ells is therefore essential for the maintenance of CD4/CD8 homeostasis in t he peripheral immune system. Unlike cell death, gamma interferon production is regulated by the p38 MAP kinase pathway in bath CD4(+) and CD8(+) T cel ls, Thus, specific aspects of CD4(+) and CD8(+) T-cell function are differe ntially controlled by the p38 MAP kinase signaling pathway.