Hangjie Zhang, Wenling Xiao, Min Zhao, Yongli Zhang, Dan Lu, Shuangshuang Lu, Qingxu Zhang, Weiyu Peng, Liumei Shu, Jie Zhang, Sai Liu, Kexin Zong, Pengyan Wang, Beiwei Ye, Danni Zhang, Shihua Li, Shuguang Tan, Peipei Liu, Yingze Zhao, Fuping Zhang, Huanyu Wang, Xuancheng Lu, George F. Gao, Jun Liu

Characterization of CD8 + T cells in immune-privileged organs of ZIKV-infected Ifnar1 −/− mice

  • Virology
  • Insect Science
  • Immunology
  • Microbiology

ABSTRACT Zika virus (ZIKV) infection caused neurological complications and male infertility, leading to the accumulation of antigen-specific immune cells in immune-privileged organs (IPOs). Thus, it is important to understand the immunological responses to ZIKV in IPOs. We extensively investigated the ZIKV-specific T cell immunity in IPOs in Ifnar1 −/− mice, based on an immunodominant epitope E 294-302 tetramer. The distinct kinetics and functions of virus-specific CD8 + T cells infiltrated into different IPOs were characterized, with late elevation in the brain and spinal cord. Single epitope E 294-302 -specific T cells can account for 20-60% of the total CD8 + T cells in the brain, spinal cord, and testicle and persist for at least 90 days in the brain and spinal cord. The E 294-302 -specific TCRαβs within the IPOs are featured with the majority of clonotypes utilizing TRAV9N-3 paired with diverse TRBV chains, but with distinct αβ paired clonotypes in 7 and 30 days post-infection. Specific chemokine receptors, Ccr2 and Ccr5 , were selectively expressed in the E 294-302 -specific CD8 + T cells within the brain and testicle, indicating an IPO-oriented migration of virus-specific CD8 + T cells after infection. Overall, this study adds to the understanding of virus-specific CD8 + T cell responses for controlling and clearing ZIKV infection in IPOs. IMPORTANCE The immune-privileged organs (IPOs), such as the central nervous system and testicles, presented pathogenicity and inflammation after Zika virus (ZIKV) infection with infiltrated CD8 + T cells. Our data show that CD8 + T cells keep up with virus increases and decreases in immune-privileged organs. Furthermore, our study provides the first ex vivo comparative analyses of the composition and diversity related to TCRα/β clonotypes across anatomical sites and ZIKV infection phases. We show that the vast majority of TCRα/β clonotypes in tissues utilize TRAV9N-3 with conservation. Specific chemokine expression, including Ccr2 and Ccr5 , was found to be selectively expressed in the E 294-302 -specific CD8 + T cells within the brain and testicle, indicating an IPO-oriented migration of the virus-specific CD8 + T cells after the infection. Our study adds insights into the anti-viral immunological characterization and chemotaxis mechanism of virus-specific CD8 + T cells after ZIKV infection in different IPOs.

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