| Autor: |
Murphy KM; Howard Hughes Medical Institute, Department of Pathology, Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Ouyang W, Szabo SJ, Jacobson NG, Guler ML, Gorham JD, Gubler U, Murphy TL |
| Jazyk: |
angličtina |
| Zdroj: |
Current topics in microbiology and immunology [Curr Top Microbiol Immunol] 1999; Vol. 238, pp. 13-26. |
| DOI: |
10.1007/978-3-662-09709-0_2 |
| Abstrakt: |
Much of our focus in understanding Th1/Th2 development has been on the signals delivered by IL-12 and IL-4 as final determinants of terminal T cell differentiation. Because extinction of IL-12 signaling in early Th2 development could potentially be important in imprinting a more permanent Th2 phenotype on a population of T cells, we have also examined various parameters regulating the IL-12 signaling pathway. Whereas IL-4 appears to repress functional IL-12 signaling through inhibition of IL-12R beta 2 expression, IFN-gamma in the mouse, and IFN-alpha in the human appear to induce IL-12R beta 2 expression and promote IL-12 responsiveness. We propose that Th1 development can be considered in two stages, capacitance and development. Capacitance would simply involve expression of IL-12R beta 1 and beta 2 subunits, regulated by TCR, IL-4 and IFNs. The second stage, development, we propose is the true IL-12 induced developmental stage, involving expression of Stat4 inducible proteins. In the human, this may also occur via IFN-alpha, which is able to activate Stat4. It is perhaps possible that all of Stat4 actions on Th1 development may be exert directly by Stat4 at the IFN-gamma gene, however we suggest that, more likely, Stat4 may act to induce Th1 development through the induction of other non-cytokine genes, whose stable expression maintains the transcriptional state of a Th1 cell. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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