HUMAN T-LYMPHOCYTE CHEMOTAXIS AND ADHESION INDUCED BY VASOACTIVE-INTESTINAL-PEPTIDE

Vasoactive intestinal peptide (VIP), a 28-amino acid peptide of the gl ucagon-secretin family, has been reported to have significant immunore gulatory properties. In the present study, we demonstrate that VIP has potent chemotactic effects on T lymphocytes. At concentrations of bet ween 10(-8) and 10(-9) M, VIP stimulated significant in vitro chemotax is of T lymphocytes from both CD4(+) and CD8(+) subsets. VIP produced more potent chemotactic effects on unstimulated T cells than on anti-C D3-activated cells. Following anti-CD3 activation, binding of I-125-la beled VIP to T cells was reduced and this correlated with a reduction in receptor number without any change in affinity. Preincubation of un stimulated 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 fibr onectin. However, VIP induced less binding of activated T cells to fib ronectin. Taken together these results suggest that VIP is a potent ch emoattractant and stimulant of adhesion for T lymphocytes. In contrast to chemokines that are more active on stimulated T cells, such as RAN TES, this neuropeptide preferentially targets unactivated T cells, sug gesting that it may play a greater role in homing and distribution of lymphocytes.