INHIBITION OF CYTOTOXICITY AND CYTOKINE RELEASE OF CD8(-SPECIFIC CYTOTOXIC T-LYMPHOCYTES BY PENTOXIFYLLINE() HIV)

HIV-specific cytotoxic T lymphocytes (CTLs) are an important component of the host immune response against HIV infection, and these cells re lease a variety of cytokines when they meet their target antigen. Sinc e the phosphodiesterase inhibitor pentoxifylline is being used as a th erapeutic agent in clinical trials of HIV infection due to its inhibit ory effect on virus replication in vitro, we examined the effect of pe ntoxifylline on cytotoxicity and cytokine secretion by HIV-specific CD 8(+) CTLs. Pentoxifylline inhibited cytotoxicity of CTLs and suppresse d interferon-gamma, tumor necrosis factor-alpha, and granulocyte macro phage colony stimulating factor release by these cells at the transcri ption level. Suppression of cytokine release resulted in reduced capac ity of the CTLs to induce HLA class I and ICAM-1 expression and to sti mulate HIV-1 replication. These results suggest that inhibition of HIV -specific CD8(+) CTLs by pentoxifylline may be therapeutically relevan t. Moreover, this study extends previous observations by demonstrating that, in addition to its ability to suppress cytokine production by m acrophages and CD4(+) T helper cells, pentoxifylline may inhibit cytot oxicity and cytokine secretion by antigen-specific CD8(+) cytotoxic T lymphocytes.