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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000294
Original Article: PDF Only

Loss of Th22 cells is associated with increased immune activation and IDO-1 activity in HIV-1 infection.

Page, Emma E MD; Greathead, Louise MSc; Metcalf, Rebecca PhD; Clark, Sally-Ann PhD; Hart, Melanie PhD; Fuchs, Dietmar D.Phil; Pantelidis, Panagiotis PhD; Gotch, Frances D.Phil; Pozniak, Anton MD; Nelson, Mark FRCP; Boasso, Adriano PhD; Gazzard, Brian FRCP; Kelleher, Peter PhD

Published Ahead-of-Print
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Abstract

BACKGROUND: Immune activation plays a key role in the immunopathogenesis of HIV-1 infection. Microbial translocation, secondary to loss of epithelial integrity and mucosal immune deficiency is believed to contribute to systemic immune activation. Interleukin (IL)-22 maintains intestinal epithelial barrier integrity and stimulates the secretion of antimicrobial peptides which limit bacterial dissemination and intestinal inflammation. IL-22 is secreted by CD4 T-helper (Th)22 cells independently of IL-17A and interferon-[gamma]. Th22 cells are characterised by the expression of chemokine receptors (CCR)4, CCR6 and CCR10.

METHODS: We analysed the frequency of Th22, Th17, Th1 and CD4 T regulatory (Treg) cells, markers of immune activation (expression of CD38 on CD8 T cells, neopterin, soluble CD14), microbial translocation (lipopolysaccharide binding protein and 16s ribosomal DNA) and indoleamine 2, 3-dioxygenase 1 (IDO-1) activity in peripheral blood of antiretroviral therapy (ART) experienced and ART-naive HIV-1 infected patients and healthy controls (HC).

RESULTS: We showed a significant reduction in the frequency of Th22 cells in HIV ART-naive patients compared to the HC and HIV ART-experienced patients. We observed a shift away from Th22 and Th17 to Treg cells, which was partially reversed by effective ART. Markers of immune activation negatively correlated with Th22 and Th17 proportions, and with Th22:Treg and Th17:Treg ratios in ART naive patients. Increased IDO-1 activity negatively correlated with Th22:Treg and Th17:Treg ratios in the ART-naive group.

CONCLUSIONS: Loss of Th22 cells and disruption in the balance of Th22 and Treg cells may contribute towards systemic immune activation and mucosal immune deficiency during HIV-1 infection.

(C) 2014 by Lippincott Williams & Wilkins

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