THE INFLUENCE OF LYMPHOCYTE COUNTS AND DISEASE PROGRESSION ON CIRCULATING AND INDUCIBLE ANTI-HIV-1 CYTOTOXIC T-CELL ACTIVITY IN HIV-1-INFECTED SUBJECTS

Objective: To evaluate specific anti-HIV cytotoxic T-lymphocyte (CTL) activity in relation to basic clinical and laboratory parameters used to follow HIV infection. Methods: Lymphocytes from HIV-1-infected subjects with different clinical and immunologic features of HIV infection were tested for circulating and inducible anti-HIV CTL activity using autologous B-lymphoblastoid cells infected with recombinant vaccinia viruses expressing the HIV gag, pol and env genes as targets. Anti-HIV CTL were induced by stimulation with HIV-infected autologous lymphoblasts in vitro. Results: We detected circulating anti-HIV CTL in asymptomatic subjects exclusively and found a significant association (P < 0.01) between CD8+ lymphocyte counts greater-than-or-equal-to 900/mul blood and detectable levels of circulating anti-HIV CTL. Subjects with circulating anti-HIV CTL also had a higher mean CD8+ lymphocyte count than those without detectable circulating activity (P < 0.001), but there was no significant difference in mean CD4+ lymphocyte count. CD8+ human histocompatibility leukocyte antigen (HLA) class I-restricted anti-HIV CTL were induced in all HIV-infected subjects tested following stimulation with HIV-infected autologous lymphoblasts in vitro. In subjects without detectable circulating anti-HIV CTL, circulating HLA-DR+ cells contributed to anti-HIV CTL activity induced by stimulation with HIV or concanavalin A in vitro. Conclusions: Circulating anti-HIV CTL activity is associated with CD8+ lymphocyte counts greater-than-or-equal-to 900/mul. Anti-HIV CTL retain proliferative and functional capacity following in vitro stimulation with HIV and interleukin-2 through all stages of HIV infection. Persistent inducible anti-HIV CTL activity in subjects with advanced HIV disease and without circulating CTL suggests impaired activation and/or proliferation of the CTL in vivo.