GM-CSF PRODUCTION BY CD4+ T-LYMPHOCYTES IS SELECTIVELY IMPAIRED DURING THE COURSE OF HIV-1 INFECTION - A POSSIBLE INDICATION OF A PREFERENTIAL LESION OF A SPECIFIC SUBSET OF PERIPHERAL-BLOOD CD4+ T-LYMPHOCYTES

The production of granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-1-beta (IL-1-beta) and tumor necrosis factor a (TNF-alpha) was evaluated in the supernatants of short-term cultures of purified CD4+ T-lymphocytes and enriched monocytes obtained from peripheral blood (PB) of 35 HIV-1 seropositive (+) asymptomatic individuals, stages I-II of the Walter Reed (WR) classification, 15 HIV (+) symptomatic patients (WR V-VI) and 40 HIV-1 seronegative normal blood donors. IL-1-beta and TNF-alpha production by either enriched monocytes or isolated CD4+ T-cells, was similar in HIV-1 (+) asymptomatic, symptomatic subjects and normal controls. GM-CSF level in enriched monocyte culture supernatants did not show any significant difference in the three groups of subjects under investigation. On the other hand, GM-CSF production by isolated CD4+ T-lymphocytes was two-fold decreased in HIV-1 (+) asymptomatic subjects and five-fold decreased in HIV-1 (+) symptomatic patients with respect to normal blood donors. The decline in GM-CSF production was clearly correlated with viral isolation from patient's PB light density mononuclear cells (r = -0.920, p<0.01). The selective and progressive decline in GM-CSF production by CD4+ T-lymphocytes, starting from early stages of HIV-1 infection, suggest a preferential lesion of a specific subset of CD4+ T-lymphocytes characterized by an intense production of GM-CSF and may contribute to explain the deranged inflammatory and immune responses which characterize the course of HIV-1 infection.