Acute activation of CD8(+) T lymphocytes in interleukin-2-treated HIV-infected patients

CD8(+) T lymphocytes play a key role in the control of HIV infection, throu gh both cytotoxic and noncytotoxic mechanisms. To study in vivo effects of interleukin-2 (IL-2) treatment on this cell compartment, the level of activ ation of CD8(+) T lymphocytes was evaluated before and just after 5-day adm inistration of IL-2 in 16 HIV-infected patients. The serum level of soluble CD25 and of soluble CD8 significantly increased following IL-2 administrat ion. The number of mRNA molecules coding for perforin and granzyme B, two e nzymes that are contained in granules of cytotoxic cells, also significantl y increased in peripheral blood mononuclear cells and in purified CD8(+) ce lls (p < .001). Variations of plasma HIV viremia and perforin gene expressi on following IL-2 administration were inversely correlated (p = .023), sugg esting that IL-2-induced activation of CD8(+) T lymphocytes contributes to limit HIV replication in vivo. In contrast to perforin and granzyme B gene expression, IL-2 administration did not increase the expression of macropha ge inhibitory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and regulated-on-a ctivation normal T-expressed and secreted (RANTES) genes. These findings in dicate that CD8(+) T lymphocytes in HIV-infected patients are acutely activ ated by IL-2 treatment, which may improve long-term control of HIV infectio n.