Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA; and Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, USA.
Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, USA.
J Leukoc Biol. 2014 Jul;96(1):55-63. doi: 10.1189/jlb.1AB0913-484RR. Epub 2014 Mar 11.
True memory CD8(+) T cells develop post antigenic exposure and can provide life-long immune protection. More recently, other types of memory CD8(+) T cells have been described, such as the memory-like CD8(+) T cells (IMP; CD44(hi)CD122(+)) that arise spontaneously in Itk(-/-) mice, which are suggested to develop as a result of IL-4 secreted by NKT-like γδ T or PLZF(+) NKT cells found in Itk(-/-) mice. However, we report here that whereas IMP CD8(+) T cell development in Itk(-/-) mice is dependent on IL-4/STAT6 signaling, it is not dependent on any γδ T or iNKT cells. Our experiments suggest that the IMP develops as a result of tuning of the CD8(+) T cell response to exogenous IL-4 and TCR triggering by ITK and challenge the current model of IMP CD8(+) T cell development as a result of NKT-like γδ T or iNKT cells. These findings suggest that some naive CD8(+) T cells may be preprogrammed by weak homeostatic TCR signals in the presence of IL-4 to become memory phenotype cells with the ability to elaborate effector function rapidly. The role of ITK in this process suggests a mechanism by which IMP CD8(+) T cells can be generated rapidly in response to infection.
真正的记忆 CD8(+) T 细胞在抗原暴露后发育，可以提供终身的免疫保护。最近，还描述了其他类型的记忆 CD8(+) T 细胞，例如记忆样 CD8(+) T 细胞（IMP；CD44(hi)CD122(+）），它们在 Itk(-/-) 小鼠中自发出现，据推测是由于 Itk(-/-) 小鼠中存在的 NKT 样 γδ T 或 PLZF(+)NKT 细胞分泌的 IL-4 而发展起来的。然而，我们在这里报告说，尽管 Itk(-/-) 小鼠中 IMP CD8(+) T 细胞的发育依赖于 IL-4/STAT6 信号，但它不依赖于任何 γδ T 或 iNKT 细胞。我们的实验表明，IMP 是由于 CD8(+) T 细胞对外源 IL-4 的反应和 ITK 触发的 TCR 进行调整而发育的，这挑战了当前关于 NKT 样 γδ T 或 iNKT 细胞导致 IMP CD8(+) T 细胞发育的模型。这些发现表明，一些幼稚的 CD8(+) T 细胞在存在 IL-4 的情况下，可能会被弱的自身稳态 TCR 信号预先编程，成为具有快速产生效应功能能力的记忆表型细胞。ITK 在这个过程中的作用表明了一种机制，通过这种机制，IMP CD8(+) T 细胞可以在感染时迅速产生。
