TYPE-1 CYTOKINE PRODUCTION AND LOW-PREVALENCE OF VIRAL ISOLATION CORRELATE WITH LONG-TERM NONPROGRESSION IN HIV-INFECTION

Cytokine production, prevalence of viral isolation, and surface marker expression of peripheral blood mononuclear cells (PBMCs) were analyze d in HIV+ individuals with different patterns of disease progression t o establish correlations between these parameters, Thus, mitogen-stimu lated in vitro production of interferon gamma (IFN-gamma) and interleu kin 2 (IL-2) (type 1 cytokines), and of IL-4 and IL-10 (type 2 cytokin es) as well as prevalence of viral isolation were evaluated in 26 HIV long-term nonprogressors (LTNPs), in 28 HIV+ patients with progressiv e HIV infection (PI), and in 24 HIV-seronegative controls (HCs), Surfa ce expression of activation and nonactivation markers was also analyze d in a group of these donors, We report that (1) IL-2 and IFN-gamma pr oduction is reduced and IL-4 and IL-10 production is increased in PI p atients compared to HCs and LTNPs; (2) prevalence of HN isolation is l ower in; LTNPs compared to PI, and the primary viral isolates in LTNPs show a slow/low (S/L) phenotype; and (3) the elevated production of t ype 2 cytokines is paralleled by an increase in CD57(+)CD4(+)CD7(-) ly mphocytes, Thus, whereas a high IL-2, high IFN-gamma/low IL-4, low IL- 10 cytokine production pattern is present in HC and in LTNP HIV+, prog ression of HIV infection is associated with a low IL-2 low IFN-gamma/h igh IL-4, high IL-10 cytokine profile; increased prevalence of HIV iso lation; and an augmented percentage of CD57(+)CD4(+)CD7(-) lymphocytes . These findings further confirm that a dominant type 1 cytokine profi le together with reduced prevalence of virus isolation is associated w ith lack of progression in HIV infection.