Huang Fei, Huang Weishan, Briggs Jessica, Chew Tina, Bai Yuting, Deol Simrita, August Avery
Department of Microbiology &Immunology, Cornell University, Ithaca, NY, 14853.
Sci Rep. 2015 Jan 8;5:7688. doi: 10.1038/srep07688.
Vaccine efficacy depends on strong long-term development of immune memory and the formation of memory CD8(+) T cells is critical for recall responses to infection. Upon antigen recognition by naïve T cells, the strength of the TcR signal influences the subsequent effector and memory cells differentiation. Here, we have examined the role of Itk, a tyrosine kinase critical for TcR signaling, in CD8(+) effector and memory T cell differentiation during Listeria monocytogenes infection. We found that the reduced TcR signal strength in Itk deficient naïve CD8(+) T cells enhances the generation of memory T cells during infection. This is accompanied by increased early Eomesodermin, IL-7Rα expression and memory precursor effector cells. Furthermore, Itk is required for optimal cytokine production in responding primary effector cells, but not secondary memory responses. Our data suggests that Itk-mediated signals control the expression of Eomesodermin and IL-7Rα, thus regulating the development of memory CD8(+) T cells, but not subsequent response of memory cells.
疫苗效力取决于免疫记忆的强大长期发展,而记忆性CD8(+) T细胞的形成对于感染的回忆反应至关重要。初始T细胞识别抗原后,TcR信号的强度会影响随后效应细胞和记忆细胞的分化。在此,我们研究了对TcR信号传导至关重要的酪氨酸激酶Itk在单核细胞增生李斯特菌感染期间CD8(+)效应T细胞和记忆T细胞分化中的作用。我们发现,Itk缺陷的初始CD8(+) T细胞中降低的TcR信号强度会增强感染期间记忆T细胞的生成。这伴随着早期Eomesodermin、IL-7Rα表达以及记忆前体效应细胞的增加。此外,Itk是应答的初始效应细胞中最佳细胞因子产生所必需的,但对二次记忆反应则不是必需的。我们的数据表明,Itk介导的信号控制Eomesodermin和IL-7Rα的表达,从而调节记忆性CD8(+) T细胞的发育,但不影响记忆细胞随后的反应。