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.

中文翻译：

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在急性HIV 1型感染过程中，肠归巢的Δ42PD1+Vδ2T细胞通过TLR4促进先天性粘膜损伤。

粘膜炎性反应和急性HIV-1感染过程中的损害背后的先天免疫细胞仍不完全了解。在这里，我们报告了急性（〜20％）HIV-1患者与慢性HIV-1患者（〜11％）和健康对照相比，肠道归巢的γδT细胞的Vδ2亚型具有明显上调的Δ42PD1（PD1亚型）。 〜2％）。在急性患者中可检测到的脂多糖之前，Δ42PD1 ⁺ Vδ2细胞的频率与促炎细胞因子和脂肪酸结合蛋白的血浆水平呈正相关。Δ42PD1的表达可由体外HIV-1感染诱导，并伴随着肠归巢受体CCR9 / CD103的高共表达。研究Δ42PD1 ⁺的作用在体内，Vδ2细胞被过继转移到自体人源化小鼠中，导致小肠炎症性损伤，这可能是由于Δ42PD1及其同源受体Toll样受体4（TLR4）相互作用所致。此外，阻滞Δ42PD1或TLR4可以成功降低Δ42PD1 ⁺ Vδ2细胞在体外诱导的细胞因子效应，以及人源化小鼠的粘膜病理学效应。因此，我们的发现揭示了由病毒诱导的肠归巢的Vδ2细胞表现出的Δ42PD1-TLR4途径，该途径可能有助于急性HIV-1感染期间的固有免疫活化和肠道发病机理。Δ42PD1 ⁺ Vδ2细胞可作为研究粘膜炎症疾病的靶标。