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标题：Development and function of T cells in T cell antigen receptor/CD3 ζ knockout mice reconstituted with FcɛRI γ
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作者：Chih-Pin Liu ; Wei-Jen Lin ; Manley Huang 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1997
卷号：94
期号：2
页码：616-621
DOI：10.1073/pnas.94.2.616
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Engagement of -{beta} T cell receptors (TCRs) induces many events in the T cells bearing them. The proteins that transduce these signals to the inside of cells are the TCR-associated CD3 polypeptides and {zeta}-{zeta} or {zeta}-{eta} dimers. Previous experiments using knockout (KO) mice that lacked {zeta} ({zeta}KO) showed that {zeta} is required for good surface expression of TCRs on almost all T cells and for normal T cell development. Surprisingly, however, in {zeta}KO mice, a subset of T cells in the gut of both {zeta}KO and normal mice bore nearly normal levels of TCR on its surface. This was because {zeta} was replaced by the Fc{varepsilon}RI {gamma} (FcR{gamma}). These cells were relatively nonreactive to stimuli via their TCRs. In addition, a previous report showed that {zeta} replacement by the FcR{gamma} chain also might occur on T cells in mice bearing tumors long term. Again, these T cells were nonreactive. To understand the consequences of {zeta} substitution by FcR{gamma} for T cell development and function in vivo, we produced {zeta}KO mice expressing FcR{gamma} in all of their T cells (FcR{gamma}TG {zeta}KO mice). In these mice, TCR expression on immature thymocytes was only slightly reduced compared with controls, and thymocyte selection occurred normally and gave rise to functional, mature T cells. Therefore, the nonreactivity of the FcR{gamma}+ lymphocytes in the gut or in tumor-bearing mice must be caused by some other phenomenon. Unexpectedly, the TCR levels of mature T cells in FcR{gamma}TG {zeta}KO mice were lower than those of controls. This was particularly true for the CD4+ T cells. We conclude that FcR{gamma} can replace the functions of {zeta} in T cell development in vivo but that TCR/CD3 complexes associated with FcR{gamma} rather than {zeta} are less well expressed on cells. Also, these results revealed a difference in the regulation of expression of the TCR/CD3 complex on CD4+ and CD8+ T cells.