Regulation of Con A-dependent cytokine production from CD4+ and CD8+ T lymphocytes by autosecretion of histamine

Previously we have shown that both CD4+ T cells and CD8+ T cells produce histamine when activated with Con A. The aim of this study was to examine whether cytokine production by these cells is regulated by autosecretion of histamine. CD4+ and CD8+ T cells were separated from spleen cells of C57BL/6 mice and mice lacking the H1 receptor (H1R) or H2R, using anti-CD4+- and anti-CD8+-coupled magnetic beads, respectively. Depletion of the H1R resulted in decreases in the release of IL-2 and IL-10 from both CD4+ and CD8+ cells and increases in the release of IL-4 from CD4+ T cells and IFN-gamma from CD8+ cells. Mice lacking the H2R showed up-regulation of IFN-gamma secretion from CD8+ cells and of IL-4 from CD4+ and CD8+ T cells. Release of IL-2 and IL-10 from CD4+ as well as CD8+ cells was down-regulated in these mice. Both CD4+ and CD8+ T cell fractions synthesized histamine, which was enhanced in the H1R-deficient CD8+ T cells. Treatment of the cells with alpha-fluoromethyl-histidine, a specific inhibitor of HDC, or histaminase increased IFN-gamma from CD8+ cells, whereas it had no appreciable effect on IL-4 secretion from CD4+ cells. These results suggest that cytokine production by CD4+ and CD8+ T lymphocytes is regulated by autosecretion of histamine.