认识一位抗癌新斗士:Vδ1T细胞
  • Vδ1 T细胞受体(TCR)为个体化的Vδ T细胞亚型;
  • Vδ2(+) T细胞表达半不变量TCR,出生时即存在,不同个体间共享;
  • Vδ1 T则不同,靶向特定抗原的Vδ1 TCR是在后天逐步富集起来的;
  • 从幼稚型分化为与CD27下调相关的效应型,保留增殖潜能和TCR敏感性,表达细胞毒标志物增多,归巢能力改变,长期持续稳定;
  • Vδ1(+) T细胞从Vδ2(+)亚群进化出不同的生物学,包括γδ TCR在高度适应性但非传统模式的抗癌、抗病毒免疫监视中发挥枢纽性作用。
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Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance

人类Vδ1T细胞克隆选择提示γδTCR依赖性过继免疫监视

10.1038/ncomms14760

2017-03-01, Article

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γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2(neg) T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2(+) T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1(+) T cells have therefore evolved a distinct biology from the Vδ2(+) subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance.

First Authors:
Martin S Davey,Carrie R Willcox

Correspondence Authors:
Benjamin E Willcox

All Authors:
Martin S Davey,Carrie R Willcox,Stephen P Joyce,Kristin Ladell,Sofya A Kasatskaya,James E McLaren,Stuart Hunter,Mahboob Salim,Fiyaz Mohammed,David A Price,Dmitriy M Chudakov,Benjamin E Willcox

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