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The Journal of Immunology, Vol 159, Issue 4 1767-1774, Copyright © 1997 by American Association of Immunologists

ARTICLES

T cell genetic background determines maintenance of IL-12 signaling: effects on BALB/c and B10.D2 T helper cell type 1 phenotype development

ML Guler, NG Jacobson, U Gubler and KM Murphy
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.

In this report, we examined the molecular basis underlying the genetic difference between BALB/c and B10.D2 T cells for T helper phenotype development in vitro. We found a strain-dependent difference in early maintenance of IL-12 responsiveness by T cells developing in vitro in unmanipulated (neutral) conditions. Thus, when activated without addition of exogenous cytokines or neutralization of endogenous cytokines, B10.D2, but not BALB/c, T cells remain responsive to IL-12 when activated for 7 days. The pattern of IL-12 responsiveness correlated with expression of the IL-12R signaling subunit, IL-12R beta2, and with IL-12-induced STAT4 phosphorylation. When activated under neutral conditions, BALB/c T cells rapidly lose IL-12R beta2 expression, STAT4 phosphorylation, and functional IL-12 responsiveness. More efficient maintenance of IL-12R beta2 expression by B10.D2 T cells activated under neutral conditions may explain the previously observed increase in IFN-gamma production relative to that of BALB/c. This difference could potentially provide greater protection from certain pathogens that do not immediately elicit strong Th1-inducing conditions via activation of the innate immune system.


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