EFFECT OF VASOACTIVE-INTESTINAL-PEPTIDE (VIP) ON CYTOKINE PRODUCTION AND EXPRESSION OF VIP RECEPTORS IN THYMOCYTE SUBSETS

Intrathymic T cell precursors undergo a programmed sequence of develop mental changes resulting in the production of mature, self-MHC restric ted, single positive T lymphocytes which migrate to the periphery. The intrathymic T cell development is controlled by various factors, incl uding cytokines and possibly neuroendocrine hormones. Our previous stu dies indicate that vasoactive intestinal peptide (VIP) inhibits IL-2 a nd IL-4 production in thymocytes through different molecular mechanism s. Thymocytes acquire the competence to express IL-2 and IL-2R during thymic development in a maturation-dependent manner. In this study we investigate the effect of VIP on IL-2 production, and the expression o f VIP-RI and VIP-R2 mRNA in different thymocyte subsets in comparison to T T cell lines. All thymocyte subsets and T cell lines tested expre ss VIP-R2. In contrast, only single positive, CD4(+)8(-) and CD4(-)8() thymocytes express VIP-R1. VIP inhibits IL-2 production in CD4(+)8() and single positive CD4(+)8(-) and CD4(-)8(+) thymocytes and in TH1 cells stimulated through the TCR. No inhibition is observed in CD3(-)4 (-)8(-) and single positive CD4(+)8(-) and CD4(-)8(+) thymocytes, or i n TH1 cells stimulated by a combination of calcium ionophores and phor bol esters. These findings suggest that VIP inhibits IL-2 production t hrough VIP-R2, and that it interferes with a TCR-connected transductio n pathway. We also investigate the expression of VIP mRNA in thymocyte subsets and T cell lines, and conclude that thymocytes as well as ant igen-specific T cells may function as VIP sources within the lymphoid organs. (C) 1997 Elsevier Science B.V.