ALTERED CYTOKINE PRODUCTION AND ACCESSORY CELL-FUNCTION AFTER HIV-1 INFECTION

We investigated cytokine production and accessory cell function in hum an macrophage hybridoma cell lines and primary monocytes after infecti on with HIV-1, HIV-1 infection induced IL-10 production in the macroph age hybridoma cell line with loss of IL-12 1 wk after infection, There were also significant increases in production of IL-10 (537 +/- 521 v s 687 +/- 625 pg/ml) while there was a reduction in IL-12 (6.3 +/- 3.1 vs 1.2 +/- 1.0 pg/ml, p = 0.021) in the primary monocytes 5 days afte r HIV-1 infection. In addition, the hybridoma cell lines and primary m onocytes failed to support PHA, Con A, PWM, or anti-CD3-induced T cell proliferation 1 wk after infection. The viability of the T cells cocu ltured with the HIV-1-infected macrophage cell lines or the primary mo nocytes as determined by propidium iodide staining was unaltered and t here was no increase in apoptosis-specific DNA strand breaks or increa sed expression of Bcl-2 in the T cells. No soluble suppressor factor w as present, since UV-inactivated supernatants from the hybridoma cell line and primary monocytes failed to inhibit mitogen- and anti-CD3-ind uced T cell proliferation, Early events in T cell activation, includin g calcium flux and phosphotyrosine kinase activity, were intact in the T cells cocultured with the HIV-1-infected hybridomas and monocytes b ut there was reduced IL-2 production, Addition of exogenous IL-2 resto red the proliferative responses, Taken together, these data suggest th at alteration of cytokine production and accessory cell function for m itogens and anti-CD3-induced T cell proliferation independent of induc tion of apoptosis, suppressor factor production, or inhibition of T ce ll signaling occurs very early after HIV-1 infection and may contribut e to the global immunosuppression observed in AIDS.