Rapaport Aaron S, Schriewer Jill, Gilfillan Susan, Hembrador Ed, Crump Ryan, Plougastel Beatrice F, Wang Yaming, Le Friec Gaelle, Gao Jian, Cella Marina, Pircher Hanspeter, Yokoyama Wayne M, Buller R Mark L, Colonna Marco
Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, 1402 South Grand Blvd, St. Louis, MO 63104, USA.
Immunity. 2015 Dec 15;43(6):1112-24. doi: 10.1016/j.immuni.2015.11.005. Epub 2015 Dec 8.
CD8(+) T cells and NK cells protect from viral infections by killing virally infected cells and secreting interferon-γ. Several inhibitory receptors limit the magnitude and duration of these anti-viral responses. NKG2A, which is encoded by Klrc1, is a lectin-like inhibitory receptor that is expressed as a heterodimer with CD94 on NK cells and activated CD8(+) T cells. Previous studies on the impact of CD94/NKG2A heterodimers on anti-viral responses have yielded contrasting results and the in vivo function of NKG2A remains unclear. Here, we generated Klrc1(-/-) mice and found that NKG2A is selectively required for resistance to ectromelia virus (ECTV). NKG2A functions intrinsically within ECTV-specific CD8(+) T cells to limit excessive activation, prevent apoptosis, and preserve the specific CD8(+) T cell response. Thus, although inhibitory receptors often cause T cell exhaustion and viral spreading during chronic viral infections, NKG2A optimizes CD8(+) T cell responses during an acute poxvirus infection.
CD8(+) T细胞和自然杀伤细胞（NK细胞）通过杀伤病毒感染细胞并分泌γ干扰素来抵御病毒感染。多种抑制性受体限制了这些抗病毒反应的强度和持续时间。由Klrc1基因编码的NKG2A是一种凝集素样抑制性受体，它在NK细胞和活化的CD8(+) T细胞上与CD94形成异二聚体表达。先前关于CD94/NKG2A异二聚体对抗病毒反应影响的研究结果相互矛盾，NKG2A在体内的功能仍不清楚。在此，我们构建了Klrc1基因敲除小鼠，并发现NKG2A是抵抗鼠痘病毒（ECTV）所选择性必需的。NKG2A在ECTV特异性CD8(+) T细胞内发挥固有功能，以限制过度活化、防止细胞凋亡并维持特异性CD8(+) T细胞反应。因此，尽管抑制性受体在慢性病毒感染期间常常导致T细胞耗竭和病毒扩散，但NKG2A在急性痘病毒感染期间优化了CD8(+) T细胞反应。
