In vitamin A deficiency multiple mechanisms establish a regulatory T helper cell imbalance with excess Th1 and insufficient Th2 function.
In hypovitaminosis A, Ab-mediated immunity is severely impaired. We reported that Trichinella spiralis infection stimulates a strong Th2 cell response in control mice but in vitamin A-deficient mice it stimulates a strong Th1 cell response. Here we investigated the immunobiologic mechanisms underlying this shift from a Th2- to a Th1-dominated response. A kinetic analysis showed that the Th1 cells developed first and IFN-gamma secretion predominated in deficient mice, whereas the Th2 cells developed later and IL-5 and IL-10 secretion predominated in control mice. The IFN-gamma-secreting cell frequencies were the same but cells from deficient mice secreted IFN-gamma sixfold faster than cells from control mice, and retinoic acid addition in vitro decreased that rate 50%. In contrast, the IL-5-secretion rates were the same but the IL-5-secreting cell frequency was lower in deficient mice than in controls, and retinoic acid addition in vitro doubled this frequency independently of its inhibitory effect on IFN-gamma. The APC from deficient mice stimulated greater IFN-gamma release than control APC and retinoic acid addition in vitro decreased this activity 50%. Together these results identify at least three vitamin A activities that balance Th1 and Th2 functions, down-regulating Th1 cell IFN-gamma secretion directly, decreasing activated APC function, and promoting Th2 cell growth and/or differentiation. In this system and perhaps others, the imbalance between regulatory Th1 and Th2 cells is one mechanism underlying poor Ab-mediated immunity in hypovitaminosis A.
Cantorna
M T
MT
Department of Biochemistry, University of Wisconsin-Madison 53706.
Nashold
F E
FE
Hayes
C E
CE
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000276:immunology*
D015848:Interleukin-5; D016753:Interleukin-10; D014212:Tretinoin; D007371:Interferon-gamma