Induction and expression of β-calcitonin gene-related peptide in rat T lymphocytes and its significance

Our previous data have shown that rat lymphocytes can synthesize calcitonin gene-related peptide (CGRP), a neuropeptide. In this study the type, characteristics, and functional role of lymphocyte-derived CGRP were investigated. The results showed that treatment with Con A (4 mu g/ml) and recombinant human IL-2 (rhIL-2; 750 U/ml) for 3-5 days induced CGRP synthesis and secretion by lymphocytes from both thymus and mesenteric lymph nodes in a time-dependent manner. Stimulation of these cells with Con A (1-8 mu g/ml) or rhIL-2 (94-1500 U/ml) for 5 days induced a significant increase in CGRP secretion in a concentration-dependent manner. The maximal secretion of CGRP with Con A by thymocytes was elevated from 104 +/- 11 to 381 +/- 44 pg/10(8) cells, and that by mesenteric lymph node lymphocytes was elevated from 83 +/- 10 to 349 +/- 25 pg/10(8) cells, respectively. The maximal CGRP secretion with rhIL-2 by thymocytes was elevated from 116 +/- 3 to 607 +/- 23 pg/10(8), and that by mesenteric lymph node lymphocytes was elevated from 117 +/- 9 to 704 +/- 37 pg/10(8) cells, respectively. The nucleotide sequencing study showed that lymphoid cells expressed beta-CGRP cDNA only. The levels of P-CGRP mRNA in mitogen-stimulated lymphocytes of both sources were also increased. However, LPS had no such effect on either source of cells. hCGRP(8-37) (2.0 mu M), a CGRP, receptor antagonist, enhanced Con A-induced proliferation and IL-2 release of thymocytes by 41.3 and 35.8% over those induced by Con A alone, respectively. The data suggest that T lymphocyte mitogens can induce the production of endogenous P-CGRP from T lymphocytes, which may partially inhibit the proliferation and IL-2 release of rat T lymphocyte under immune challenges.