The role of lek gene in T cell proliferation and differentiation was investigated with transgenic mice carrying human lek cDNA whose expression was regulated by the promoter of mouse H-2Kb and the enhancer element of mouse IgH. RNase protection assay revealed that the lek transgene was expressed in the thymus and spleen, whereas immunoblot analysis demonstrated that amounts of p56/ck in freshly isolated lymphoid organs were almost equal between transgenic mice and negative littermates. Cell-surface marker analyses of the thymocytes and peripheral lymphocytes revealed no remarkable difference between both groups. Notable finding is that the thymocytes from transgenic mice showed a significant proliferative response to the stimulation with IL-2, but not the thymocytes from negative littermates. Further analysis revealed that CD4+8- single positive thymocytes proliferated in response to IL-2. While surface expression levels of IL-2Ra and IL-2Rβ of these CD4+8- thymocytes from transgenic and control mice were almost equal before stimulation with IL-2, the expression of IL-2Rβ was induced only in transgenic thymocytes after stimulation with IL-2. Immunoblot analysis demonstrated that the expression of p56/ck of transgenic thymocytes was not down-reguated at 4 hr after stimulaion with IL-2, whereas p56/ck of control ones were not detectable any more at 4 hr after stimulation with IL-2. Moreover, in vitro kinase assay substantiated such unchanged expression of p56/cA in the thymocytes from transgenic mice: the kinase activities of p56/ck did not decrease in thymocytes from transgenic mice after stimulation with IL-2, while kinase activities of control ones were significantly down-regulated by stimulation of IL-2. These results suggested that a significant proliferative response found in the thymocytes from β&-transgenic mice after the stimulation with IL-2 was caused by a constitutive expression of p56/ck in these thymocytes even after the stimulation. Our findings, therefore, support a possibility that p56/c6 may play a role in the IL-2R-mediated signaling system in CD4+8~ thymocytes.
|ジャーナル||MICROBIOLOGY and IMMUNOLOGY|
|出版ステータス||出版済み - 1993|
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