SEROTONIN REGULATION OF T-CELL SUBPOPULATIONS AND OF MACROPHAGE ACCESSORY FUNCTION

The role of serotonin as an immune modulator was investigated by measu ring the functional competence of T cells from control mice versus fro m mice whose intracellular stores of serotonin had been depleted by pr etreatment with p-chlorophenylalanine (PCPA). While the proportions of splenic CD4(+) and CD8(+) T cells isolated from control and PCPA-trea ted mice were similar, the level of expression of the alpha-chain inte rleukin-2 receptor (IL-2R) was reduced on splenic CD4(+) cells but not on CD8(+) cells. Culture with the T-cell mitogen concanavalin A (Con A) failed to induce expression of the IL-2R on either CD4(+) or CD8(+) cells of PCPA-treated mice, although IL-2R was induced on control cel ls, The proliferative response to Con A by these spleen cells from PCP A-treated mice was also reduced compared to that by control spleen cel ls. Both expression of IL-2R and proliferation in response to Con A by spleen cells from serotonin-depleted mice were increased or completel y restored by supplementation of the cultures with serotonin. Studies to identify the mechanisms for the reduction in T-cell activation when serotonin levels were reduced implicated a defect in the capacity of macrophages from PCPA-treated mice to provide accessory help for T-cel l activation. Splenic macrophages from control mice were able to resto re the blastogenic capability of lymphocytes from PCPA-treated mice, a lthough macrophages from PCPA-treated mice were unable to support norm al lymphocyte blastogenesis unless the cultures were supplemented with serotonin. These results show the requirement of autologous serotonin for optimal T-cell activation and suggest the importance of serotonin in macrophage accessory function for T-cell activation.