Enhanced delayed-type hypersensitivity and diminished immediate-type hypersensitivity in mice lacking the inducible VPAC(2) receptor for vasoactive intestinal peptide.

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  • Author(s): Goetzl EJ;Goetzl EJ; Voice JK; Shen S; Dorsam G; Kong Y; West KM; Morrison CF; Harmar AJ
  • Source:
    Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2001 Nov 20; Vol. 98 (24), pp. 13854-9. Date of Electronic Publication: 2001 Nov 06.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0027-8424 (Print) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Hypersensitivity, Delayed/*immunology ; Hypersensitivity, Immediate/*immunology ; Receptors, Vasoactive Intestinal Peptide/*immunology ; Vasoactive Intestinal Peptide/*immunology; Animals ; Interferon-gamma/metabolism ; Interleukin-4/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Vasoactive Intestinal Peptide/genetics ; Receptors, Vasoactive Intestinal Peptide, Type II ; Th1 Cells/immunology ; Th2 Cells/immunology
    • Abstract:
      Vasoactive intestinal peptide (VIP) and its G protein-coupled receptors, VPAC(1)R and VPAC(2)R, are prominent in the immune system and regulate many aspects of T cell-dependent immunity. In mouse T cells, VPAC(1)R is expressed constitutively, whereas VPAC(2)R is induced by immune stimuli. VPAC(2)R-null (VPAC(2)R(-/-)) 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(+)) and T cells bearing CD4, CD8, and CD28. Hapten-evoked cutaneous delayed-type hypersensitivity (DTH) was significantly enhanced in VPAC(2)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 > or =70% lower in VPAC(2)R-null mice than in wild-type controls. Cytokine production by splenic CD4(+) T cells, stimulated with adherent anti-CD3 plus anti-CD28 antibodies, revealed higher levels of IL-2 (mean = 3-fold) and IFN-gamma (mean = 3-fold), and lower levels of IL-4 (mean = one-fifth) in VPAC(2)R-null mice than wild-type controls. Loss of VIP-VPAC(2)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.
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    • Grant Information:
      R01 AI029912 United States AI NIAID NIH HHS; R37 AI029912 United States AI NIAID NIH HHS; AI29912 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Receptors, Vasoactive Intestinal Peptide)
      0 (Receptors, Vasoactive Intestinal Peptide, Type II)
      207137-56-2 (Interleukin-4)
      37221-79-7 (Vasoactive Intestinal Peptide)
      82115-62-6 (Interferon-gamma)
    • Publication Date:
      Date Created: 20011108 Date Completed: 20020108 Latest Revision: 20231105
    • Publication Date:
      20231105
    • Accession Number:
      PMC61131
    • Accession Number:
      10.1073/pnas.241503798
    • Accession Number:
      11698667