STIMULATION OF SPLENIC T-LYMPHOCYTE FUNCTION BY ENDOGENOUS SEROTONIN AND BY LOW-DOSE EXOGENOUS SEROTONIN

The modulatory effects of endogenous serotonin on splenic T-cell activ ity were investigated using two distinct approaches. The first approac h showed that pretreatment of mice with p-cholorphenylalanine (PCPA) t o deplete intracellular stores of serotonin reduced the capacity of th eir splenic T cells to proliferate and to express interleukin-2 recept or (IL-2R) in response to concanavalin A (Con A). These responses coul d be restored by the addition of serotonin to the spleen cell cultures . In contrast, PCPA treatment did not effect stimulation of spleen cel ls to produce IL-2. The second approach showed that T-cell proliferati on to Con A as well as to IL-2 was diminished by the presence of antag onists to the serotonin-2 receptor (5-HT2R). The effects of low doses (100 ng/ml) of exogenously added serotonin on functions of normal sple en cells were also examined. At this low dose, serotonin stimulated sp lenic T-cell proliferation in response to IL-2, and enhanced both prol iferation and IL-2 production in response to a suboptimal concentratio n of Con A. These results show autologous serotonin to be required for T-cell activation and that the activation of suboptimally stimulated T cells can be augmented with low doses of exogenously added serotonin . These data also suggest that the positive regulation of T-cell funct ion by serotonin is mediated through 5-HT2R.