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Department of Biological Sciences, Rutgers University, Newark, NJ 07102; and
Departamento Biologia Celular, Universidad Complutense, Madrid, Spain
Vasoactive intestinal peptide (VIP) and the pituitary adenylate
cyclase-activating polypeptide (PACAP), two structurally related
neuropeptides produced within the lymphoid microenvironment, modulate
several immunologic functions. We have recently demonstrated that VIP
and PACAP enhance the macrophage costimulatory activity for naive
CD4+ T cells exposed to allogeneic or anti-CD3 stimuli
through the differential regulation of the B7 costimulatory molecules.
In this study, we report on the role of VIP and PACAP on macrophage B7
expression and costimulatory function for Ag-primed CD4+ T
cells, and on the macrophage-induced regulation of Th1/Th2
differentiation in vitro and in vivo. VIP and PACAP up-regulate the
costimulatory activity of macrophages for Ag-primed CD4+ T
cells. VIP-/PACAP-treated macrophages gain the ability to induce
Th2-type cytokines such as IL-4 and IL-5 and reduce Th1-type cytokines
such as IFN-
and IL-2. In vivo administration of VIP or PACAP in
Ag-immunized mice reduce the numbers of IFN--secreting cells and
enhance the numbers of IL-4-secreting cells. One of the consequences of
the VIP-/PACAP-induced shift in cytokine profile is a change in the
Ag-specific Ig isotype, increasing IgG1 and decreasing IgG2a levels.
Finally, the preferential differentiation into Th2 effector cells after
Ag stimulation induced by VIP-/PACAP-treated macrophages is mediated
through the up-regulation of B7.2 expression.
This article has been cited by other articles:
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  E. Gonzalez-Rey, P. Anderson, and M. Delgado Emerging roles of vasoactive intestinal peptide: a new approach for autoimmune therapy Ann Rheum Dis, November 1, 2007; 66(suppl_3): iii70 - iii76. [Abstract] [Full Text] [PDF]
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 E. Gonzalez-Rey, A. Chorny, F. O'Valle, and M. Delgado Adrenomedullin Protects from Experimental Arthritis by Down-Regulating Inflammation and Th1 Response and Inducing Regulatory T Cells Am. J. Pathol., January 1, 2007; 170(1): 263 - 271. [Abstract] [Full Text] [PDF]
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 W. Sun, J. Hong, Y. C. Q. Zang, X. Liu, and J. Z. Zhang Altered expression of vasoactive intestinal peptide receptors in T lymphocytes and aberrant Th1 immunity in multiple sclerosis Int. Immunol., December 1, 2006; 18(12): 1691 - 1700. [Abstract] [Full Text] [PDF]
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E. Gonzalez-Rey, A. Fernandez-Martin, A. Chorny, J. Martin, D. Pozo, D. Ganea, and M. Delgado Therapeutic Effect of Vasoactive Intestinal Peptide on Experimental Autoimmune Encephalomyelitis: Down-Regulation of Inflammatory and Autoimmune Responses Am. J. Pathol., April 1, 2006; 168(4): 1179 - 1188. [Abstract] [Full Text] [PDF]
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 V. Sharma, M. Delgado, and D. Ganea Granzyme B, a New Player in Activation-Induced Cell Death, Is Down-Regulated by Vasoactive Intestinal Peptide in Th2 but Not Th1 Effectors J. Immunol., January 1, 2006; 176(1): 97 - 110. [Abstract] [Full Text] [PDF]
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 D. Miotto, P. Boschetto, I. Bononi, E. Zeni, G. Cavallesco, L.M. Fabbri, and C.E. Mapp Vasoactive intestinal peptide receptors in the airways of smokers with chronic bronchitis Eur. Respir. J., December 1, 2004; 24(6): 958 - 963. [Abstract] [Full Text] [PDF]
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S. Kodali, W. Ding, J. Huang, K. Seiffert, J. A. Wagner, and R. D. Granstein Vasoactive Intestinal Peptide Modulates Langerhans Cell Immune Function J. Immunol., November 15, 2004; 173(10): 6082 - 6088. [Abstract] [Full Text] [PDF]
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 D. POZO and M. DELGADO The many faces of VIP in neuroimmunology: a cytokine rather a neuropeptide? FASEB J, September 1, 2004; 18(12): 1325 - 1334. [Abstract] [Full Text] [PDF]
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 H. Keino, T. Kezuka, M. Takeuchi, N. Yamakawa, T. Hattori, and M. Usui Prevention of Experimental Autoimmune Uveoretinitis by Vasoactive Intestinal Peptide Arch Ophthalmol, August 1, 2004; 122(8): 1179 - 1184. [Abstract] [Full Text] [PDF]
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Y. Zafirova, M. Yordanov, and R. Kalfin Antiarthritic effect of VIP in relation to the host resistance against Candida albicans infection Int. Immunol., August 1, 2004; 16(8): 1125 - 1131. [Abstract] [Full Text] [PDF]
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 M. Delgado, D. Pozo, and D. Ganea The Significance of Vasoactive Intestinal Peptide in Immunomodulation Pharmacol. Rev., June 1, 2004; 56(2): 249 - 290. [Abstract] [Full Text] [PDF]
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 M. Delgado, A. Reduta, V. Sharma, and D. Ganea VIP/PACAP oppositely affects immature and mature dendritic cell expression of CD80/CD86 and the stimulatory activity for CD4+ T cells J. Leukoc. Biol., June 1, 2004; 75(6): 1122 - 1130. [Abstract] [Full Text] [PDF]
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E. Kuroda and U. Yamashita Mechanisms of Enhanced Macrophage-Mediated Prostaglandin E2 Production and Its Suppressive Role in Th1 Activation in Th2-Dominant BALB/c Mice J. Immunol., January 15, 2003; 170(2): 757 - 764. [Abstract] [Full Text] [PDF]
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 A. Metwali, A. M. Blum, D. E. Elliott, and J. V. Weinstock IL-4 inhibits vasoactive intestinal peptide production by macrophages Am J Physiol Gastrointest Liver Physiol, July 1, 2002; 283(1): G115 - G121. [Abstract] [Full Text] [PDF]
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 D. Ganea and M. Delgado VASOACTIVE INTESTINAL PEPTIDE (VIP) AND PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) AS MODULATORS OF BOTH INNATE AND ADAPTIVE IMMUNITY Crit. Rev. Oral. Biol. Med., May 1, 2002; 13(3): 229 - 237. [Abstract] [Full Text]
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M. Delgado and D. Ganea Cutting Edge: Is Vasoactive Intestinal Peptide a Type 2 Cytokine? J. Immunol., March 1, 2001; 166(5): 2907 - 2912. [Abstract] [Full Text] [PDF]
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E. Kuroda, T. Sugiura, K. Okada, K. Zeki, and U. Yamashita Prostaglandin E2 Up-Regulates Macrophage-Derived Chemokine Production but Suppresses IFN-Inducible Protein-10 Production by APC J. Immunol., February 1, 2001; 166(3): 1650 - 1658. [Abstract] [Full Text] [PDF]
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D. Vaudry, B. J. Gonzalez, M. Basille, L. Yon, A. Fournier, and H. Vaudry Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: From Structure to Functions Pharmacol. Rev., June 1, 2000; 52(2): 269 - 324. [Abstract] [Full Text] [PDF]
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M. Delgado and D. Ganea Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide Inhibit Antigen-Induced Apoptosis of Mature T Lymphocytes by Inhibiting Fas Ligand Expression J. Immunol., February 1, 2000; 164(3): 1200 - 1210. [Abstract] [Full Text] [PDF]
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