Retinoid repletion of vitamin A-deficient mice restores IgG responses.
Vitamin A-deficient (A-) mice produce poor IgG antibody responses due to a helper T cell dysfunction. We performed retinoid repletion studies to determine the minimum dietary retinyl acetate dose and the most active retinoid for supporting immune function. Dietary retinyl acetate repletion at 2 (R2 group) or 4 (R4 group) microgram/g diet restored serum retinol in A- mice to vitamin A-sufficient (A+) control levels within 24 h. However, in R4 mice, liver retinyl palmitate was restored about twofold faster than in R2 mice; liver retinyl palmitate reached A+ control levels by d 30 in R4 mice but not in R2 mice. We challenged the mice with antigen 24 h post repletion; the R4 mice gave an IgG1 response equal to that of A+ controls, but the R2 mice were comparable with the A- controls. We also compared four retinoids for IgG1 response restoration in vitro; 1 nmol/L retinoic acid fully repleted A- cell IgG1 responses and helper T cell frequencies to the unsupplemented A+ control levels. Retinoic acid was at least 10-fold more active than retinyl acetate or retinaldehyde, and 100-fold more active than retinol. Collectively, our results suggest that retinoic acid is probably the physiologically important metabolite for sustaining IgG immune responses in vivo. We discuss the possible relationship between liver retinyl palmitate levels and availability of retinoic acid to support immune function.
Chun
T Y
TY
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison 53706.
Carman
J A
JA
Hayes
C E
CE
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects; D004032:Diet; D004224:Diterpenes; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D000084562:Retinyl Esters; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014212:Tretinoin / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000097:blood / Q000188:drug therapy / Q000276:immunology*
D004224:Diterpenes; D007074:Immunoglobulin G; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate; D014212:Tretinoin