Serotonin regulation of T-cell subpopulations and of macrophage accessory function.
The role of serotonin as an immune modulator was investigated by measuring the functional competence of T cells from control mice versus from mice whose intracellular stores of serotonin had been depleted by pretreatment with p-chlorophenylalanine (PCPA). While the proportions of splenic CD4+ and CD8+ T cells isolated from control and PCPA-treated mice were similar, the level of expression of the alpha-chain interleukin-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 cells. The proliferative response to Con A by these spleen cells from PCPA-treated mice was also reduced compared to that by control spleen cells. Both expression of IL-2R and proliferation in response to Con A by spleen cells from serotonin-depleted mice were increased or completely 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-cell activation. Splenic macrophages from control mice were able to restore the blastogenic capability of lymphocytes from PCPA-treated mice, although macrophages from PCPA-treated mice were unable to support normal 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.
Young
M R
MR
Research Service, Hines VA Hospital, Hines, Illinois.
Matthews
J P
JP
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D012701:Serotonin / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D012701:Serotonin; D010134:Fenclonine