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Published on: June 30, 2013
Molecular Analyses Define Vα7.2-Jα33+ MAIT Cell Depletion in HIV Infection: A Case-Control Study
James E Ussher1, Prabhjeet Phalora, Cormac Cosgrove
1From the Peter Medawar Building for Pathogen Research (JEU, PP, CC, PG, REP, CBW, PK), University of Oxford, Oxford, UK; Department of Microbiology and Immunology (JEU, RFH), University of Otago, Dunedin, New Zealand; Ragon Institute of MGH, MIT and Harvard (CC), Cambridge, Massachusetts, USA; Division of Infectious Diseases (AR), University Hospital Berne and University of Berne, Berne; Division of Infectious Diseases and Hospital Epidemiology and Institute of Medical Virology (HFG), University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Abstract:
Mucosal-associated invariant T (MAIT) cells are an abundant antibacterial innate-like lymphocyte population. There are conflicting reports as to their fate in HIV infection. The objective of this study was to determine whether MAIT cells are truly depleted in HIV infection. In this case-control study of HIV-positive patients and healthy controls, quantitative real-time polymerase chain reaction was used to assess the abundance of messenger RNA (mRNA) and genomic DNA (gDNA) encoding the canonical MAIT cell T cell receptor (Vα7.2-Jα33). Comparison was made with flow cytometry. Significant depletion of both Vα7.2-Jα33 mRNA and gDNA was seen in HIV infection. Depletion of Vα7.2+CD161++ T cells was confirmed by flow cytometry. In HIV infection, the abundance of Vα7.2-Jα33 mRNA correlated most strongly with the frequency of Vα7.2+CD161++ cells. No increase was observed in the frequency of Vα7.2+CD161- cells among CD3+CD4- lymphocytes. MAIT cells are depleted from blood in HIV infection as confirmed by independent assays. Significant accumulation of a CD161- MAIT cell population is unlikely. Molecular approaches represent a suitable alternative to flow cytometry-based assays for tracking of MAIT cells in HIV and other settings.
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