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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 DPhil; Pantelidis, Panagiotis PhD; Gotch, Frances DPhil*; Pozniak, Anton MD§; Nelson, Mark FRCP§; Boasso, Adriano PhD*; Gazzard, Brian FRCP§; Kelleher, Peter PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 November 2014 - Volume 67 - Issue 3 - p 227–235
doi: 10.1097/QAI.0000000000000294
Basic and Translational Science

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 22 maintains intestinal epithelial barrier integrity and stimulates the secretion of antimicrobial peptides that limit bacterial dissemination and intestinal inflammation. Interleukin 22 is secreted by CD4 T-helper (Th)22 cells independently of interleukin 17A and interferon γ. Th22 cells are characterized by the expression of chemokine receptors (CCR)4, CCR6, and CCR10.

Methods: We analyzed 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 activity in peripheral blood of antiretroviral therapy (ART)-experienced and ART-naive HIV-1–infected patients and healthy controls.

Results: We showed a significant reduction in the frequency of Th22 cells in HIV ART-naive patients compared with the healthy controls 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 indoleamine 2,3-dioxygenase 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 toward systemic immune activation and mucosal immune deficiency during HIV-1 infection.

*Department of Medicine, Imperial College, London, United Kingdom;

Division of Biological Chemistry, Biocenter, Medical University, Innsbruk, Austria;

Department of Infection and Immunity, Imperial College NHS Trust, London, United Kingdom; and

§Department of HIV and Sexual Health, Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.

Correspondence to: Peter Kelleher, PhD, Department of Infection and Immunity, Immunology Department, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, United Kingdom (e-mail:

Supported by the St Stephen's AIDS Trust (2-year clinical fellow salary to E.E.P.), the European AIDS Treatment Network (WP8#036 to E.E.P.), the British HIV Association (2009 Research Award to E.E.P.).

The authors have no conflicts of interest to disclose.

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Received January 25, 2014

Accepted June 11, 2014

© 2014 by Lippincott Williams & Wilkins