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. 2017 Oct;2(10):1389-1402.
doi: 10.1038/s41564-017-0006-5. Epub 2017 Aug 14.

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

Allen Ka Loon Cheung  1 , Hau-Yee Kwok  1 , Yiru Huang  1 , Min Chen  1   2 , Yufei Mo  1 , Xilin Wu  1 , Ka-Shing Lam  1 , Hoi-Kuan Kong  3 , Terrence Chi Kong Lau  3 , Jingying Zhou  1 , Jingjing Li  1 , Lin Cheng  1   4 , Boon Kiat Lee  1 , Qiaoli Peng  4 , Xiaofan Lu  5 , Minghui An  6 , Hui Wang  4 , Hong Shang  6 , Boping Zhou  4 , Hao Wu  5 , Aimin Xu  7 , Kwok-Yung Yuen  1 , Zhiwei Chen  8   9
Affiliations

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

Allen Ka Loon Cheung et al. Nat Microbiol. 2017 Oct.

Abstract

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.

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