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IL-7-induced proliferation of peripheral Th17 cells is impaired in HAART-controlled HIV infection

Côté, Sandra C.a,*; Stilla, Alanaa,b,*; Burke Schinkel, Stephanie C.a; Berthoud, Tamara K.a,b; Angel, Jonathan B.a,b,c

doi: 10.1097/QAD.0000000000002164
CONCISE COMMUNICATION
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Objectives: Th17 cells are key regulators of functional immunity in mucosal tissues, including the gut-associated lymphoid tissue (GALT), an important site of immune impairment in HIV infection. During HIV infection, Th17 cells are lost in large numbers from the GALT. Despite the recovery of peripheral CD4+ T cells that accompanies suppression of viral replication with HAART, Th17 cells in GALT are not completely restored. IL-7 is essential for the survival and proliferation of T cells, but its signaling through its receptor IL-7Rα (CD127), is impaired in CD8+ T cells and thymocytes during HIV infection. We set out to determine if decreased CD127 expression or impaired CD127 signaling may be the cause of Th17 impairment in HAART-controlled HIV infection.

Design: Healthy and HIV+ donors on HAART were selected for this study of Th17 cell function in HIV.

Methods: Peripheral CD4+ T cells and Th17 cells were isolated using magnetic beads, then stimulated with IL-7. CD127 expression and the phosphorylation of signaling molecules was determined using flow cytometry. Proliferation was determined with a CFSE dilution assay.

Results: CD127 was not decreased on Th17 cells from HAART-controlled HIV+ individuals, in fact, the percentage of Th17 cells that express CD127 was increased in treated HIV+ individuals. Furthermore, Th17 cells from HAART-controlled individuals, have normal IL-7-induced STAT5 and Bcl-2 responses, but vastly decreased proliferative responses.

Conclusion: This reduced IL-7 responsiveness may explain the lack of Th17 cell recovery and ongoing systemic immune activation that persists despite well treated HIV infection.

aThe Ottawa Hospital Research Institute, Ottawa

bDepartment of Biochemistry, Microbiology, and Immunology, The University of Ottawa, Ottawa

cDivision of Infectious Diseases, The Ottawa Hospital, Ottawa, Ontario, Canada.

Correspondence to Jonathan B. Angel, MD, FRCP, Ottawa Hospital - General Campus, 501 Smyth Road, Box 223, Ottawa, ON K1H 8L6, Canada. E-mail: jangel@ohri.ca

Received 13 September, 2018

Revised 18 December, 2018

Accepted 15 January, 2019

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