Roles of vasoactive intestinal peptide (VIP) in the expression of different immune phenotypes by wild-type mice and T cell-targeted type II VIP receptor transgenic mice.
Vasoactive intestinal peptide (VIP) and its two G protein-coupled receptors, VPAC1 and VPAC2, are quantitatively prominent and functionally critical in the immune system. Transgenic (T) mice constitutively expressing VPAC2 selectively in CD4 T cells, at levels higher than those found after maximal induction in CD4 T cells of wild-type (N) mice, have elevated blood concentrations of IgE, IgG1, and eosinophils; enhanced immediate-type hypersensitivity; and reduced delayed-type hypersensitivity. In contrast, VPAC2-null (K) mice manifest decreased immediate-type hypersensitivity and enhanced delayed-type hypersensitivity. The phenotypes are attributable to opposite skewing of the Th2/Th1 cytokine ratio, but no studies were conducted on the roles of T cell-derived VIP and altered expansion of the Th subsets. Dependence of the Th phenotype of T mice, but not of N or K mice, on T cell-derived VIP now is proven by showing that eliminating VIP from TCR-stimulated T cell cultures with VIPase IgG normalizes the elevated number of IL-4-secreting CD4 T cells, decreases the secretion of IL-4 and IL-10, and increases the secretion of IFN-gamma. Flexible responsiveness of CD4 T cells from N and K mice, but not T mice, to exogenous VIP in vitro and in vivo is shown by increased numbers of IL-4-secreting CD4 T cells, greater secretion of IL-4 and IL-10, and lesser secretion of IFN-gamma after TCR stimulation with VIP. The level of VIP recognized by CD4 T cells thus is a major determinant of the relative contributions of Th subsets to the immune effector phenotype.
Voice
Julia K
JK
Department of Medicine, University of California Medical Center, San Francisco, CA 94143, USA.
Grinninger
Carola
C
Kong
Yvonne
Y
Bangale
Yogesh
Y
Paul
Sudhir
S
Goetzl
Edward J
EJ
D000818:Animals; D017151:Antibodies, Catalytic / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000235:genetics; D006969:Hypersensitivity, Immediate / Q000235:genetics; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010452:Peptide Biosynthesis / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D018005:Receptors, Vasoactive Intestinal Peptide / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
D017151:Antibodies, Catalytic; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide