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


METHODS
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-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.


CONCLUSIONS
These results suggest that cytokine production by CD4+ and CD8+ T lymphocytes is regulated by autosecretion of histamine.
Sonobe
Y
Y
Department of Animal Cell Function, Biotechnology and Bioscience Center, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Nakane
H
H
Watanabe
T
T
Nakano
K
K
D006631:Amine Oxidase (Copper-Containing) / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011969:Receptors, Histamine H1 / Q000172:deficiency; D011970:Receptors, Histamine H2 / Q000172:deficiency; D015854:Up-Regulation
D016207:Cytokines; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D008762:Methylhistidines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; C028309:alpha-fluoromethylhistidine; D007371:Interferon-gamma; D006631:Amine Oxidase (Copper-Containing); D006640:Histidine Decarboxylase