Effect of HIV infection on the frequency of cytokine-secreting cells in human peripheral blood.

A selective decrease in type 1 cytokine secretion by in vitro stimulated peripheral blood cells is reportedly associated with disease progression in HIV-infected individuals. To examine whether a similar change in cytokine secretion occurs under physiologic conditions in vivo, sensitive and specific ELIspot assays were used to compare the phenotype and frequency of PBMC spontaneously producing interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma) in 83 HIV-infected subjects and 60 normal controls. Phenotypic analysis of freshly isolated cytokine-secreting cells showed that T cells were the primary source of IL-2, IL-4, and IFN-gamma while CD14+ macrophages/monocytes were the dominant source of IL-10 in vivo. The number of peripheral blood mononuclear cells (PBMC) spontaneously secreting both type 1 and type 2 cytokines was significantly reduced in HIV-infected patients versus controls. The magnitude of this decrease did not correlate with disease severity. Changes in IL-2-secreting cell number correlated with CD4 count, while changes in the frequency of IFN-gamma-secreting cells correlated with disease duration. These findings do not support the contention that a selective reduction in type 1 cytokine production correlates with disease progression.