CD8+ T lymphocytes producing Th2-type cytokines (Tc2) in HIV-infected individuals

Unusual high proportions of CD8+ T-cell clones able to produce IL-4, but no IFN-gamma (Tc2 cells), were generated from both skin biopsies and peripheral blood of HIV-infected individuals in advanced phase of infection. Tc2 cells showed unusual phenotypic and functional features, such as CD30 expression, B-cell helper activity for IgE synthesis and reduced cytolytic potential. Cloning CD8+ T-cell from HIV-infected individuals in autologous feeder cells resulted in a marked increase of CD8+ T-cell clones showing a Tc2 profile. The addition in bulk culture before cloning of both IL-12 and a neutralizing anti-IL-4 antibody dramatically reversed the cytokine profile of CD8+ T-cell clones of HIV-infected individuals to the classic Tc1 pathway. Finally, cloning CD8+ T-cells from healthy HIV-seronegative donors in the presence of feeder cells from HIV-infected individuals resulted in the development of enhanced proportions of CD8+ T-cell clones able to produce IL-4. These data suggest that CD8+ T-cells from HIV-infected individuals can develop into Tc2 cells likely because of either the defective production of IL-12 by HIV-infected macrophages and/or other microenvironmental conditions favoring early IL-4 production. The Tc2 shift during HIV infection may play some role in the reduced defence against viral infections, including HIV itself, in patients with AIDS.