Abnormal regulation of IFN-gamma secretion in vitamin A deficiency.
T lymphocytes from vitamin A-deficient (A-) mice show a decreased ability to stimulate B lymphocytes for Ag-specific secondary IgG1 responses in vivo and in vitro. Experiments reported here traced the molecular basis for this functional defect to an overproduction of IFN-gamma by A- CD4+ T cells compared with cells from A-sufficient (A+) mice. Secretion of IL-2 and IL-4 by cells from A- and A+ mice was equivalent. Retinoic acid supplementation in vitro decreased IFN-gamma secretion from A- T cells, indicating that IFN-gamma production is retinoid-responsive. Adding IFN-gamma neutralizing antibodies to cultures established with cells from immune A- mice substantially increased IgG1 production, whereas IL-4 addition moderately increased IgG1 production. Adding retinoic acid to the cultures either at initiation, or 48 h later, fully restored IgG1 production by A- cultures to the level of A+ control cultures. These results are consistent with a role for vitamin A in negatively regulating IFN-gamma secretion.
Carman
J A
JA
College of Agricultural and Life Sciences, University of Wisconsin-Madison, Department of Biochemistry 53706.
Hayes
C E
CE
D000818:Animals; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis / Q000494:pharmacology; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000276:immunology / Q000378:metabolism*
D007074:Immunoglobulin G; D007376:Interleukin-2; D015847:Interleukin-4; D014212:Tretinoin; D007371:Interferon-gamma