Reduction of IFN-gamma and IL-2 production by peripheral lymphocytes of HIV-exposed seronegative subjects

Objectives: In order to evaluate the role played by cytokine profile as a c o-factor involved in the resistance to HIV infection in couples serodiscord ant for HIV, we studied HIV-seronegative subjects with multiple unprotected sexual exposures. Design and methods: Twenty-one HIV-exposed seronegative subjects (HEPS), th eir 21 HIV-seropositive partners and 10 HIV-seronegative unexposed individu als were studied for T helper (Th) types 1-2 cell pattern and CCR5 receptor . Results: Twelve out of 21 HIV-seropositive partners of HEPS showed a CD4 ce ll count below 200 lymphocytes/mu l. HIV strains were isolated from periphe ral blood mononuclear cells (PBMC) in 17 patients (81%): seven subjects wit h syncytium-inducing strains and 10 with non-syncytium-inducing isolates. L ow Th1 cytokine production and high levels of IL-4 were detected in HIV-ser opositive subjects. A significant reduction of IL-2 and IFN-gamma expressio n in the CD4 and CD8 cells of HEPS was found compared with HIV-seronegative unexposed individuals. Similar levels of low IL-4 were present in both HEP S and controls. The partial deletion of a single allele (wild type/Delta 32 ) of CCR5 was found in only one HEPS. Conclusion: The downregulated Th1 profile we observed in HEPS could be rela ted to a cellular anergy state with a protective role in the transmission r ate of HIV. Low levels of IL-2 and IFN-gamma could be involved in a low-gra de activation state of CD4 lymphocytes. A decrease of IFN-gamma levels coul d render macrophage cells incapable of antigen presentation, thus resulting in a reduction of the cell-to-cell spread of Introduction infection. (C) 1 999 Lippincott Williams & Wilkins.