PROGRESSIVE AND SELECTIVE IMPAIRMENT OF IL-3 AND IL-4 PRODUCTION BY PERIPHERAL-BLOOD CD4+ T-LYMPHOCYTES DURING THE COURSE OF HIV-1 INFECTION

The amounts of interleukin 3 (IL-3), interleukin 4 (IL-4), tumor necrosis factor alpha (TNF-alpha), and tumor necrosis factor beta (TNF-beta) were evaluated by immunoenzymatic assays in the supernatant of short-term cultures of whole mononuclear cells and purified CD4+ T-lymphocytes, obtained from the peripheral blood (PB) of 35 HIV-1(+) asymptomatic individuals (stages I-II of the Walter Reed Classification), 20 HIV-1(+) symptomatic patients (WR V-VI), and 40 HIV-1(-) blood donors. TNF-alpha and TNF-beta production was similar in HIV-1(+) asymptomatic individuals, HIV-1(+) symptomatic patients, and HIV-1(-) controls. On the other hand, IL-3 and IL-4 production by either whole mononuclear cells or isolated CD4+ T-cells was decreased approximately 2-fold (p < 0.01) in HIV-1(+) asymptomatic subjects with respect to HIV-1(-) blood donors and was very low or almost absent in HIV-1(+) symptomatic individuals. The reduced IL-3 and IL-4 production in HIV-1-infected subjects correlated not only with the stage of the disease, but also with signs of active viral replication in PB cells, monitored by gag p24 antigen in plasma and viral isolation from PB mononuclear cells. This selective and progressive impairment in IL-3 and IL-4 production by CD4+ T-lymphocytes of HIV-1-infected subjects may contribute to explain the hematopoietic abnormalities and the derangement of the inflammatory/immune system characteristic of AIDS.