Analysis of the Characteristics of TIGIT-Expressing CD3CD56+NK Cells in Controlling Different Stages of HIV-1 Infection

Xin Zhang, Xiaofan Lu, Ka Loon Allen CHEUNG, Qiuyue Zhang, Zhiying Liu, Zhen Li, Lin Yuan, Rui Wang, Yan Liu, Bin Tang, Huan Xia, Hao Wu, Tong Zhang*, Bin Su

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGIT+NK cells in acute infection was positively associated with HIV-1 viral load (r = 0.53, P = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96CD226+ cells diminished among total NK cells, TIGIT+NK and TIGITNK cells, while CD96+CD226 cells expanded. Reduced CD96CD226+ cells and elevated CD96+CD226 cells among NK cells especially TIGITNK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2ANKG2C+NK cells, with a significantly higher proportion than in NKG2A+NKG2CNK cells. Moreover, the frequencies of TIGIT+NK cells were positively associated with the frequencies of NKG2ANKG2C+NK cells in acute infection (r = 0.62, P < 0.0001), chronic infection (r = 0.37, P = 0.023) and healthy donors (r = 0.36, P = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGIT+NK cells were detected compared to TIGITNK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGIT+NK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGITNK cells in both acute and chronic infection. Moreover, the functionalities of TIGIT+NK cells were lower than those of TIGITNK cells, except for TNF-αCD107a+IFN-γNK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.

Original languageEnglish
Article number602492
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 26 Feb 2021

Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

User-Defined Keywords

  • HIV-1
  • immune exhaustion
  • immune responses
  • NK cells
  • TIGIT

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