Gut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection

Allen Ka Loon Cheung, Hau Yee Kwok, Yiru Huang, Min Chen, Yufei Mo, Xilin Wu, Ka Shing Lam, Hoi Kuan Kong, Terrence Chi Kong Lau, Jingying Zhou, Jingjing Li, Lin Cheng, Boon Kiat Lee, Qiaoli Peng, Xiaofan Lu, Minghui An, Hui Wang, Hong Shang, Boping Zhou, Hao WuAimin Xu, Kwok Yung Yuen, Zhiwei Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

13 Citations (Scopus)


The innate immune cells underlying mucosal inflammatory responses and damage during acute HIV-1 infection remain incompletely understood. Here, we report a Vδ2 subset of gut-homing γδ T cells with significantly upregulated Δ42PD1 (a PD1 isoform) in acute (~20%) HIV-1 patients compared to chronic HIV-1 patients (~11%) and healthy controls (~2%). The frequency of Δ42PD1+Vδ2 cells correlates positively with plasma levels of pro-inflammatory cytokines and fatty-acid-binding protein before detectable lipopolysaccharide in acute patients. The expression of Δ42PD1 can be induced by in vitro HIV-1 infection and is accompanied by high co-expression of gut-homing receptors CCR9/CD103. To investigate the role of Δ42PD1+Vδ2 cells in vivo, they were adoptively transferred into autologous humanized mice, resulting in small intestinal inflammatory damage, probably due to the interaction of Δ42PD1 with its cognate receptor Toll-like receptor 4 (TLR4). In addition, blockade of Δ42PD1 or TLR4 successfully reduced the cytokine effect induced by Δ42PD1+Vδ2 cells in vitro, as well as the mucosal pathological effect in humanized mice. Our findings have therefore uncovered a Δ42PD1–TLR4 pathway exhibited by virus-induced gut-homing Vδ2 cells that may contribute to innate immune activation and intestinal pathogenesis during acute HIV-1 infection. Δ42PD1+Vδ2 cells may serve as a target for the investigation of diseases with mucosal inflammation.

Original languageEnglish
Pages (from-to)1389-1402
Number of pages14
JournalNature Microbiology
Early online date14 Aug 2017
Publication statusPublished - Oct 2017

Scopus Subject Areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology


Dive into the research topics of 'Gut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection'. Together they form a unique fingerprint.

Cite this