Johnston J A, Taub D D, Lloyd A R, Conlon K, Oppenheim J J, Kevlin D J
Laboratory of Molecular Immunoregulation, Program Resources, Inc./Dyncorp, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702.
J Immunol. 1994 Aug 15;153(4):1762-8.
Vasoactive intestinal peptide (VIP), a 28-amino acid peptide of the glucagon-secretin family, has been reported to have significant immunoregulatory properties. In the present study, we demonstrate that VIP has potent chemotactic effects on T lymphocytes. At concentrations of between 10(-8) and 10(-9) M, VIP stimulated significant in vitro chemotaxis of T lymphocytes from both CD4+ and CD8+ subsets. VIP produced more potent chemotactic effects on unstimulated T cells than on anti-CD3-activated cells. Following anti-CD3 activation, binding of 125I-labeled VIP to T cells was reduced and this correlated with a reduction in receptor number without any change in affinity. Preincubation of unstimulated T cells with VIP produced increases in adhesion to ICAM and VCAM integrins. In addition, VIP pretreatment significantly increased unstimulated T cell adhesion to the extracellular matrix protein fibronectin. However, VIP induced less binding of activated T cells to fibronectin. Taken together these results suggest that VIP is a potent chemoattractant and stimulant of adhesion for T lymphocytes. In contrast to chemokines that are more active on stimulated T cells, such as RANTES, this neuropeptide preferentially targets unactivated T cells, suggesting that it may play a greater role in homing and distribution of lymphocytes.
血管活性肠肽（VIP）是一种胰高血糖素-促胰液素家族的28个氨基酸的肽，据报道具有显著的免疫调节特性。在本研究中，我们证明VIP对T淋巴细胞具有强大的趋化作用。在10^(-8)至10^(-9) M的浓度范围内，VIP刺激了来自CD4+和CD8+亚群的T淋巴细胞显著的体外趋化作用。VIP对未刺激的T细胞产生的趋化作用比对抗CD3激活的细胞更强。抗CD3激活后，125I标记的VIP与T细胞的结合减少，这与受体数量的减少相关，而亲和力没有任何变化。用VIP预孵育未刺激的T细胞会增加其对ICAM和VCAM整合素的粘附。此外，VIP预处理显著增加了未刺激的T细胞对细胞外基质蛋白纤连蛋白的粘附。然而，VIP诱导激活的T细胞与纤连蛋白的结合较少。综上所述，这些结果表明VIP是一种强大的T淋巴细胞趋化剂和粘附刺激剂。与对刺激的T细胞更活跃的趋化因子（如RANTES）不同，这种神经肽优先作用于未激活的T细胞，表明它可能在淋巴细胞的归巢和分布中发挥更大作用。
