AUGMENTATION OF HIV-SPECIFIC LYMPHOPROLIFERATION IN HIV-INFECTED INDIVIDUALS BY TRAT - A NOVEL T-CELL IMMUNOPOTENTIATING AGENT

Objective: To evaluate the potential of TraT to restore HIV-specific c ell-mediated immunity. Design: CD4+ T cell-associated antiviral and re call antigen-specific lymphoproliferative responses are generally impa ired or absent in HIV-infected individuals. Methods: Using peripheral blood mononuclear cells (PBMC) from a group of asymptomatic and sympto matic HIV-infected individuals, we compared the immunomodulatory effec ts of exogenous interleukin-2 (IL-2) with the effects elicited by the bacterial integral membrane protein, TraT. Results: Exogenous IL-2 enh anced lymphoproliferation induced by an immunodominant synthetic HIV g p41 analogue, gp41{8} (amino acids 593-604), in four out of 10 asympto matics and six out of 19 symptomatics. In contrast, TraT acted synergi stically with gp41{8} to augment HIV-specific proliferation with highe r frequency and greater magnitude than exogenous IL-2. Moreover, this TraT-mediated enhancement of HIV-specific lymphoproliferation occurred in the majority of HIV-infected individuals, irrespective of CD4+ T-c ell count in peripheral blood or disease status, and thus appears not to be major histocompatibility complex-restricted. TraT also augmented lymphoproliferation induced by well-known recall antigens and other l ess immunodominant HIV analogues. Conclusions: These findings suggest that TraT, in combination with HIV-derived peptides, could be used to maintain or restore cell-mediated immune functions of HIV-infected ind ividuals, as well as cellular immune functions in individuals sufferin g from other immunodeficiency disorders.