Analysis of the Immunomodulatory Properties of the Secretin-Glucagon Family of Peptides on Mouse Lymphoid Cell Functions and the Demonstration of Specific Receptors on T Cells

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Abstract
The ability of members of the secretin-glucagon family of peptides to modulate the responses of mouse lymphoid cells stimulated with Concanavalin A (Con A), Lipopolysaccharide (LPS) and alloantigens was determined. It was observed that vasoactive intestinal peptide (VIP) and peptide having NH2-terminal histidine and COOH-terminal Isoleucine (PHI) inhibited the incorporation of 3H-methyl-thymidine by cells stimulated with Con A (55% inhibition) or alloantigen-bearing cells (40% inhibition). Secretin was approximately 10,000 less effective as an immunomodulator. Other members of the neuropeptide family, including glucagon and gastric inhibitory peptide, were ineffective in affecting mitogenesis elicited by Con A (20% inhibition). Lipopolysaccaride stimulated spleen cells were refractory to modulation by all members of the secretin-glucagon family of peptides (less than 5% modulation). The inhibition measured was concentration dependent over the range of 10−6 to 10−16 M. A peptide fragment of VIP encompassing amino acid residues 10–28, although capable of modulating in vitro responses, was 30–50% less effective than intact VIP. In addition, a VIP specific binding assay for mouse lymphoid cells was described. The binding of 125I-vIP to lymph node cells was rapid, saturable and reversible. Apparent equilibrium was reached within 15 minutes and nonspecific binding, measured as 125I-VIP binding in the presence of an excess (2 × 10−7 M) of native VIP, did not exceed 25% of the total binding. In competitive experiments using VIP related peptides, PHI but not gastic inhibitory peptide, glucagon or secretin was able to significantly inhibit 125I-VIP binding. PHI had only one-eighth of the competitive capacity of native VIP. Scatchard analyses indicated the existence of a single class of high affinity receptors on lymph node cells (KD=3.46 nM; 26,000 sites/cell). 125I-VIP specific binding to purified T cells (14%) was markedly higher than to B cells (3% binding). Thymocytes bound less than 2% of the label and had relatively few VIP binding sites (8,000) as compared with purified T cells (45,000 sites/cell). There was variability in the ability of various T cells tumors and functional T cell clones to bind 125I-VIP. The role of VIP as a physiological modulator of T cell activation is discussed.