{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:57:22Z","timestamp":1789711042325,"version":"4.0.1"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,11,20]]},"abstract":"<jats:p>\n                    Vasoactive intestinal peptide (VIP) and its G protein-coupled receptors, VPAC\n                    <jats:sub>1<\/jats:sub>\n                    R and VPAC\n                    <jats:sub>2<\/jats:sub>\n                    R, are prominent in the immune system and regulate many aspects of T cell-dependent immunity. In mouse T cells, VPAC\n                    <jats:sub>1<\/jats:sub>\n                    R is expressed constitutively, whereas VPAC\n                    <jats:sub>2<\/jats:sub>\n                    R is induced by immune stimuli. VPAC\n                    <jats:sub>2<\/jats:sub>\n                    R-null (VPAC\n                    <jats:sub>2<\/jats:sub>\n                    R\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice on a C57BL\/6 background are shown here to have normal basic immune characteristics, including serum Ig concentrations, blood levels of all leukocytes, and spleen number of total T cells (CD3\n                    <jats:sup>+<\/jats:sup>\n                    ) and T cells bearing CD4, CD8, and CD28. Hapten-evoked cutaneous delayed-type hypersensitivity (DTH) was significantly enhanced in VPAC\n                    <jats:sub>2<\/jats:sub>\n                    R-null mice compared with age- and sex-matched wild-type mice. In contrast, generation of IgE anti-hapten antibodies and active cutaneous anaphylaxis were \u226570% lower in VPAC\n                    <jats:sub>2<\/jats:sub>\n                    R-null mice than in wild-type controls. Cytokine production by splenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, stimulated with adherent anti-CD3 plus anti-CD28 antibodies, revealed higher levels of IL-2 (mean = 3-fold) and IFN-\u03b3 (mean = 3-fold), and lower levels of IL-4 (mean = one-fifth) in VPAC\n                    <jats:sub>2<\/jats:sub>\n                    R-null mice than wild-type controls. Loss of VIP-VPAC\n                    <jats:sub>2<\/jats:sub>\n                    R maintenance of the normal ratio of Th2\/Th1 cytokines thus leads to a state of enhanced DTH and depressed immediate-type hypersensitivity, which may alter both host defense and susceptibility to immune-mediated diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.241503798","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:07Z","timestamp":1027679707000},"page":"13854-13859","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":106,"title":["Enhanced delayed-type hypersensitivity and diminished immediate-type hypersensitivity in mice lacking the inducible VPAC\n                    <sub>2<\/sub>\n                    receptor for vasoactive intestinal peptide"],"prefix":"10.1073","volume":"98","author":[{"given":"Edward J.","family":"Goetzl","sequence":"first","affiliation":[{"name":"Departments of Medicine and Immunology, University of California Medical Center, San Francisco, CA 94143-0711; 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