T cell genetic background determines maintenance of IL-12 signaling: effects on BALB/c and B10.D2 T helper cell type 1 phenotype development
| Autor: | M L Güler, N G Jacobson, U Gubler, K M Murphy |
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| Rok vydání: | 1997 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 159:1767-1774 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.159.4.1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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