ROLE OF INTERLEUKIN-10 IN T-HELPER CELL DYSFUNCTION IN ASYMPTOMATIC INDIVIDUALS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS

The loss of T helper cell (TH) function in asymptomatic HIV type 1-inf ected individuals occurs before the decline in CD4(+) T cells. At leas t part of the loss in TH function results from changes in immunoregula tory cytokine profiles. To investigate the role of IL-10 in such dysre gulation, we tested whether: (a) expression of IL-10-specific mRNA wou ld be upregulated in PBMC from asymptomatic, HIV-infected (HIV+) indiv iduals; (b) PBMC from these same individuals would produce increased l evels of IL-10 when stimulated in vitro with phytohemagglutinin; and ( c) defective antigen-specific TH function could be restored by anti-IL -10 antibody. We observed that IL-10-specific mRNA was marginally upre gulated, and increased levels of IL-10 were produced by PBMC from HIV individuals compared with PBMC from uninfected individuals, Those ind ividuals whose TH function was more severely compromised produced high er levels of IL-10. Additionally, defective antigen-specific TH functi on in vitro could be reversed by anti-IL-10 antibody, including the re sponse to HIV envelope synthetic peptides. Furthermore, the antigen-sp ecific TH responses of HIV-uninfected PBMC could be reduced with IL-10 , a process reversed by anti-IL-10. These results confirm that the ear ly loss of TH function in HIV+ individuals is due at least in part to cytokine-induced immune dysregulation, and support the hypothesis of a switch from a predominant type 1 state to a predominant type 2 condit ion in HIV infection.