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 developmental changes resulting in the production of mature, self-MHC restricted, single positive T lymphocytes which migrate to the periphery. The intrathymic T cell development is controlled by various factors, including cytokines and possibly neuroendocrine hormones. Our previous studies indicate that vasoactive intestinal peptide (VIP) inhibits IL-2 and IL-4 production in thymocytes through different molecular mechanisms. 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 of VIP-R1 and VIP-R2 mRNA in different thymocyte subsets in comparison to T cell lines. All thymocyte subsets and T cell lines tested express 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 in TH1 cells stimulated by a combination of calcium ionophores and phorbol esters. These findings suggest that VIP inhibits IL-2 production through VIP-R2, and that it interferes with a TCR-connected transduction pathway. We also investigate the expression of VIP mRNA in thymocyte subsets and T cell lines, and conclude that thymocytes as well as antigen-specific T cells may function as VIP sources within the lymphoid organs.
Xin
Z
Z
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Jiang
X
X
Wang
H Y
HY
Denny
T N
TN
Dittel
B N
BN
Ganea
D
D
D000818:Animals; D001483:Base Sequence; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000494:pharmacology*
D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate