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Immune activation has been observed in HIV-infected and uninfected Africans, among whom it is thought to modify interaction between the immune system and HIV. To characterize this phenomenon accurately, in-depth immunologic analyses were performed in a rural African population. Freshly drawn peripheral blood mononuclear cells (PBMCs) of HIV-infected African (from Gulu, Uganda) and Italian antiviral-naive patients and those of uninfected Ugandan and Italian study subjects were analyzed. Individuals were matched for age and sex and determined to be free from parasitic infections. Intracellular cytokines were measured in mitogen (M)- and gp160 peptides + staphylococcal enterotoxin B and alpha CD28 (env)-stimulated T lymphocytes. Interferon (IFN)-gamma-producing CD8(+) T cells were quantified in an enzyme-linked immunosorbent assay. Results showed that M-stimulated production of interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha increases in CD4(+) and CD8(+) cells of African infected patients and uninfected study subject; and that env-stimulated IL-10 and TNF-alpha production is increased in CD8(+) T lymphocytes of African HIV-infected patients. M- and env-stimulated IFN-gamma-producing CD8(+) T cells were reduced in African participants and not increased by preincubation with alpha IL-10 monoclonal antibody. This is the first set of data that has reported immune activation in rural Africa by single-cell analysis of cytokine production. These results help in defining the immunologic background to be considered in the design of therapeutic and vaccine-based approaches to HIV infection in an African setting.

Objective: Immune activation induced by chronic infections, dietary limitations, and poor hygienic conditions is suggested to be present in African HIV infection and is at the basis of the hypothesis that HIV infection in Africa could be prevalently associated with immunopathogenetic mechanisms. Very limited data are nevertheless available supporting this theory, and in particular no data are reported on functional and phenotypic analyses performed on fresh peripheral blood mononuclear cells (PBMC) of African HIV-infected patients living in Africa., Design: Immunological and virological parameters were analysed in fresh PBMC of HIV-infected African and Italian patients with advanced HIV disease and comparable CD4 and CD8 counts, sex, and age. Both functional (antigen- and mitogen-stimulated cytokine production) and phenotypic (activation markers; markers preferentially expressed by T helper (Th) type 2 cells or by memory and naive cells) analyses were performed. Results were compared with those of HIV-seronegative African and Italian controls. HIV plasma viraemia was analysed by competitive polymerase chain reaction (PCR) and branched DNA techniques., Results: (1) The production of mitogen-stimulated IFN-gamma and TNF-alpha as well as the production of env peptide-stimulated IFN-gamma, TNF-alpha, and IL-10 are increased in African HIV infection; (2) the expression of activation and Th2-associated markers is augmented in African HIV infection as is the memory/naive ratio; (3) mitogen-stimulated IFN-gamma and IL-10 production, as well as the expression of activation and Th2-associated markers and the memory/naive ratio, are augmented in African compared with Italian controls; and (4) plasma viraemia is reduced in African compared with Italian HIV-infected individuals., Conclusions: These results, which are the first to be reported on fresh material from African HIV-infected patients living in Africa, indicate that HIV disease is associated with an abnormal immune hyperactivation and may be accompanied in these patients by lower loads of virus, and show that such activation is present even in HIV-seronegative controls.