MAIT cells are innate-like lymphocytes enriched in mucosal tissues, liver, and peripheral blood, contributing to protection against pathogens. Alcohol abuse and HIV infection independently reduce circulating MAIT cells. To assess their combined impact, we studied peripheral blood MAIT cells in heavy drinkers without overt liver disease (ALC), people with HIV (PWH) on ART, PWH on ART with heavy drinking (HIV-ALC), and healthy donors (HD). MAIT cell frequencies were significantly reduced in ALC (median 0.56, IQR 0.22-1.44; p=0.001), HIV (0.43, 0.20-0.97; p<0.001), and HIV-ALC (0.30, 0.14-0.74; p<0.001) vs HD (1.52, 0.74-2.71), accompanied by increased apoptotic MAIT cells. MAIT cells in HIV and HIV-ALC expressed elevated levels of activation markers (CD38, HLA-DR), with HIV-ALC also having higher CD69 levels than HIV and HD. Activated MAIT cells in HIV-ALC positively correlated with disease severity (prolonged prothrombin time, total bilirubin) and trended inversely with CD4% and CD4/CD8 ratio. However, no correlate was observed with cytokines linked to MAIT cell activation/function (IFN-α, IL-7, IL-12, IL-15, IL-17, IL-18, IL-23, IFN-γ, TNF-α). They also did not correlate with levels of blood biomarkers of gut injury/microbial translocation (TFF3, REG3α, LBP), monocyte/macrophage activation (sCD14, sCD163), and systemic inflammation (CRP). Conclusion: Peripheral blood MAIT cells in HIV-ALC were severely depleted, yet highly activated, and associated with disease severity.
Peripheral mucosal-associated invariant T (MAIT) cells are severely depleted in HIV-positive heavy alcohol users
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Date: May 6 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1