Center for Comparative Medicine, University of California, Davis, CA 95616.
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616.
Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10416-10421. doi: 10.1073/pnas.1808339115. Epub 2018 Sep 25.
While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against infection. Using an epitope-tagged vaccine strain of , we found that effective protection correlated with expanded -specific memory CD4 T cells in circulation and nonlymphoid tissues. However, naive mice that previously shared a blood supply with vaccinated partners lacked T cell memory with characteristics of tissue residence and did not acquire robust protective immunity. Using a YFP-IFN-γ reporter system, we identified Th1 cells in the liver of immunized mice that displayed markers of tissue residence, including P2X7, ARTC2, LFA-1, and CD101. Adoptive transfer of liver memory cells after ARTC2 blockade increased protection against highly virulent bacteria. Taken together, these data demonstrate that noncirculating memory Th1 cells are a vital component of immunity to infection and should be the focus of vaccine strategies.
虽然 CD4 Th1 细胞对于抵抗巨噬细胞内感染是必需的，但 Th1 细胞的过继转移不足以预防感染。我们使用一种表位标记的疫苗株，发现有效的保护与循环和非淋巴组织中扩大的 - 特异性记忆 CD4 T 细胞相关。然而，以前与接种疫苗的伙伴共享血液供应的幼稚小鼠缺乏具有组织驻留特征的 T 细胞记忆，并且没有获得强大的保护性免疫。使用 YFP-IFN-γ报告系统，我们在免疫小鼠的肝脏中鉴定出具有组织驻留标记的 Th1 细胞，包括 P2X7、ARTC2、LFA-1 和 CD101。ARTC2 阻断后过继转移肝脏记忆细胞可增加对高毒力细菌的保护。综上所述，这些数据表明，非循环记忆 Th1 细胞是对感染免疫的重要组成部分，应成为疫苗策略的重点。
