SEROTONIN MODULATES IMMUNE FUNCTION IN T-CELLS FROM HIV-SEROPOSITIVE SUBJECTS

We have shown earlier increased intracellular levels of cAMP in periph eral lymphocytes from HIV-seropositive subjects and that a chemically induced decrease in this level increases cell proliferation and cytoto xicity. Others have shown that serotonin indirectly decreases intracel lular cAMP levels in normal peripheral lymphocytes. In this study, we show that addition of serotonin decreases intracellular levels of cAMP in lymphocytes from EW-seropositive subjects and significantly increa ses the proliferative capacity in vitro. However, the effect of seroto nin varies with the initial proliferative response; e.g., those with t he highest initial responses have the highest increases. An increase i n IL-2 production may be a part of this mechanism since addition of se rotonin to in vitro cultures of PHA-stimulated cells increases the exp ression of mRNA for IL-2 and IFN-gamma. The effect on lymphocyte proli feration was most likely mediated through the serotonin 5HT1a receptor because similar results could be obtained by using DPAT, a specific a ctivator of this receptor. Changes in the expression of 5HT1a receptor s as judged by the expression of mRNA could not explain why serotonin in vitro had a stronger enhancing effect on cell proliferation in some HIV-seropositive individuals than in others. (C) 1997 Academic Press.