CD8-CELL-MEDIATED SUPPRESSION OF HIV LONG TERMINAL REPEAT-DRIVEN GENE-EXPRESSION IS NOT ASSOCIATED WITH IMPROVED CLINICAL STATUS( T)

Objectives: To determine the associations between the suppression of H IV-1 long terminal repeat (LTR)-mediated gene expression by CD8+ T-cel l supernatants and clinical correlates of well-being, including CD4+ a nd CD8+ T-cell counts, beta-chemokine production and clinical stage of disease. Methods: Culture supernatants of activated CD8+ T cells deri ved from a panel of HIV-1-infected subjects were assessed for their ab ility to suppress HIV-1 LTR-mediated chloramphenicol acetyl transferas e (CAT) expression. The percentage suppression of gene expression was correlated with CD4+ and CD8+ T-cell counts and clinical stage of infe ction. Some individuals within this group were followed at 2-3 month i ntervals over time to assess the consistency of the suppression. Selec ted CD8+ T-cell culture supernatants of diverse suppressive ability we re screened for the levels of the beta-chemokines macrophage inflammat ory protein (MIP)-1 alpha, MIP-1 beta and RANTES. Results: The ability of CD8+ T cells of HIV-1-infected subjects to suppress HIV-1 LTR-medi ated gene expression did not show a dependence upon high CD4+ T-cell c ounts or on the clinical stage or duration of infection. The ability t o suppress gene expression did show a relationship with higher CD8+ T- cell counts and correlated with the levels of beta-chemokines in the c ulture supernatants. In contrast, strong suppression was mediated by C D8+ T-cell supernatants from some subjects with very low CD8+ T-cell c ounts and relatively low chemokine levels. Conclusions: Although the s uppression of gene expression by CD8+ T-cell culture supernatants show ed statistical correlation with beta-chemokine levels and with higher CD8+ T-cell count, no correlation could be found with correlates of cl inical wellbeing.