Genetic control of IL-12 responsiveness as a critical determinant of th1 development and resistance to leishmania major

M. L. Guler, J. D. Gorham, C. S. Hsieh, S. J. Szabo, K. M. Murphy

Research output: Contribution to journalArticle

Abstract

Mouse strains such as BALB/c and B10.D2 develop different Th responses to Leishmania Major and consequently are differentially susceptible to the pathogen. Using an in vitro model system, a difference in maintenance of IL-12 responsiveness in T cells from BALB/c and B10.D2 mice was found. Although T cells from either strain could initially respond to IL-12, BALB/c T cells lost IL-12 responsiveness upon antigen activation in vitro, even when cultured in the presence of B10.D2 T cells, which consistently maintained IL-12 responsiveness. The intrinsic ability of B10.D2 T cells to maintain IL-12 responsiveness correlated with their increased sensitivity to IFNy, which upregulated components of the IL-12 signaling pathway. Therefore, downregulation of IL-12 signaling components may account for the BALB/c-specific Inability to develop IL-12 induced Th1 phenotype in vitro. This developmental defect may explain L. mayor susceptibility in this mouse strain.

Original languageEnglish
Pages (from-to)A1036
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

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