INTERLEUKIN-10 GENE-EXPRESSION INDUCED BY HIV-1 TAT AND REV IN THE CELLS OF HIV-1-INFECTED INDIVIDUALS

The role of cytokines in the regulation and function of the immune sys tem is of great importance. In human immunodeficiency virus (HIV) infe ction, with progressive deterioration of cell-mediated immune response , cytokines are dysregulated. We have therefore investigated cytokine mRNA expression in type-1 and type-2 helper T cells of HIV-seropositiv e (HIV+) individuals, stimulated with mitogen (leukoagglutinin) and HI V-1 Tat and Rev peptides, previously found to induce proliferative T-c ell responses in these individuals. Reverse transcriptase-polymerase c hain reaction (RT-PCR) was used to detect interleukin 2 (IL-2), interf eron gamma (IFN-gamma), IL-4, and IL-10 mRNAs. There was no difference in the mRNA expression of these cytokines when the cells of HIV-infec ted or noninfected individuals were polyclonally stimulated with the m itogen, as all cytokine mRNAs were detected in both groups. Baseline c ytokine expression of unstimulated cells was, however, different in th ese two groups: the cells of HIV+ persons did not show comparable expr ession of mRNAs to HIV-seronegative (HIV-) individuals. When the cells of HIV+ individuals were stimulated with the peptides, 70% of the cas es showed IL-10 mRNA expression, 20% IFN-gamma, and 10% IL-2, with no detection of IL-4 mRNA in any of the cases. Our results thus show that HIV-specific T-cell antigens induce production of IL-10 in HIV-infect ed individuals. The increase in IL-10 demonstrated here may have a rol e in hyperactivation of B cells, as well as in immunosuppression of T cells often seen in HIV-infected individuals.