In vitamin A deficiency multiple mechanisms establish a regulatory T helper cell imbalance with excess Th1 and insufficient Th2 function

Margherita Teresa-Anna Cantorna, Faye E. Nashold, Colleen E. Hayes

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Abstract

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-γ secretion predominated in deficient mice, whereas the Th2 cells developed later and IL- 5 and IL-10 secretion predominated in control mice. The IFN-γ-secreting cell frequencies were the same but cells from deficient mice secreted IFN-γ 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-γ. The APC from deficient mice stimulated greater IFN-γ 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-γ 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.

Original languageEnglish (US)
Pages (from-to)1515-1522
Number of pages8
JournalJournal of Immunology
Volume152
Issue number4
Publication statusPublished - Feb 15 1994

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All Science Journal Classification (ASJC) codes

  • Immunology

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