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

Abstract

Objectives: 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.

Materials: 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.

Results: 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-γ from CD8+ cells. Mice lacking the H2R showed up – regulation of IFN-γ 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 α-fluoromethyl-histidine, a specific inhibitor of HDC, or histaminase increased IFN-γ from CD8+ cells, whereas it had no appreciable effect on IL-4 secretion from CD4+ cells.

Conclusions: These results suggest that cytokine production by CD4+ and CD8+ T lymphocytes is regulated by autosecretion of histamine.