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Polarized Development of Memory Cell-Like IFN--Producing Cells in the Absence of TCR -Chain

Division of Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010

TCR/CD3 complex-mediated signals play critical roles in regulating CD4⁺ Th cell differentiation. In this report, we have examined the in vivo role of a key TCR/CD3 complex molecule -chain in regulating the differentiation of Th cells. We have studied T cells from -chain-deficient mice (KO mice), -chain-bearing mice (⁺ mice), and from KO mice expressing a FcR chain transgene (FcRTG, KO mice). Our results demonstrated that, compared with those of control mice, CD4⁺ T cells and not CD8⁺ T cells from KO mice were polarized into IFN--producing cells. Some of these IFN--producing cells could also secrete IL-10. Interestingly, KO mouse T cells produced IFN- even after they were cultured in a Th2 condition. Our studies to determine the molecular mechanisms underlying the polarized IFN- production revealed that the expression level of STAT4 and T-bet were up-regulated in freshly isolated T cells from KO mice. Further studies showed that noncultured KO mice CD4⁺ T cells and thymocytes bore a unique memory cell-like CD44^high, CD62L^low/neg phenotype. Altogether, these results suggest that, in the absence of the -chain, CD4⁺ T cells develop as polarized IFN--producing cells that bear a memory cell-like phenotype. The -chain-bearing T cells may produce a large amount of IFN- only after they are cultured in a condition favoring Th1 cell differentiation. This study may provide important implications for the down-regulation of -chain in T cells of patients bearing a variety of tumors, chronic inflammatory and infectious diseases.

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