Aims: Our previous work has shown that lymphocytes synthesize and secrete catecholamines (CAs), which regulate lymphocyte proliferation and apoptosis. In the present study, we explored the effect of the lymphocyte-derived CAs on differentiation and function of T helper (Th) cells. Methods: Lymphocytes were separated from the mesenteric lymph nodes of mice and stimulated by concanavalin A (Con A). These cells were treated with alpha-methyl-p- tyrosine (α-MT), an inhibitor of tyrosine hydroxylase (TH) that is a rate-limiting enzyme for synthesis of CAs, and pargyline, an inhibitor of monoamine oxidase that degrades CAs. Results: Treatment of Con A-stimulated lymphocytes with α-MT (10–6m) reduced CAs both in the cultured lymphocytes and in the culture supernatants. Simultaneously, α-MT upregulated expression of mRNAs and proteins of T-box expressed in T cells (T-bet) and interferon-γ (IFN-γ) but downregulated expression of mRNAs and proteins of GATA binding protein 3 (GATA-3) and interleukin-4 (IL-4) in Con A-activated lymphocytes. In contrast, pargyline (10–6m) increased intracellular and supernatant CA contents in Con A-activated lymphocytes. Meanwhile, the treatment with pargyline downregulated expression of T-bet and IFN-γ but upregulated expression of GATA-3 and IL-4 in these lymphocytes. Conclusion: CAs synthesized and secreted by lymphocytes regulate differentiation and function of Th cells, with an effect facilitating the shift of Th1/Th2 balance toward Th2 polarization.

Keywords:
Catecholamines, T helper cells, T-bet, GATA-3, Interferon-γ, Interleukin-4
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2012
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