title: Attrition of TCR Vα7.2+ CD161++ MAIT cells in HIV-tuberculosis co-infection is associated with elevated levels of PD-1 expression.
abstract: Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8(+) T cells co-expressing the semi-invariant TCR Vα7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV-1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161(++)CD8(+) T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naïve HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono- and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.
authors.affiliation: Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia; Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Alireza
authors.initials: A
authors.lastname: Saeidi
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Vicky L
authors.initials: VL
authors.lastname: Tien Tien
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Rami
authors.initials: R
authors.lastname: Al-Batran
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Haider A
authors.initials: HA
authors.lastname: Al-Darraji
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Hong Y
authors.initials: HY
authors.lastname: Tan
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Yean K
authors.initials: YK
authors.lastname: Yong
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sasheela
authors.initials: S
authors.lastname: Ponnampalavanar
authors.affiliation: Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Muttiah
authors.initials: M
authors.lastname: Barathan
authors.affiliation: Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Devi V
authors.initials: DV
authors.lastname: Rukumani
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Abdul W
authors.initials: AW
authors.lastname: Ansari
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA 30329, United States of America.
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Velu
authors.affiliation: Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.affiliation: Molekylär Virologi, Institutionen för Klinisk Och Experimentell Medicin, Linköpings Universitet, 581 85 Linköping, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia; Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D060085:Coinfection / Q000188:drug therapy / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D054399:Receptors, CCR6 / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; C106311:CCR6 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell; D054399:Receptors, CCR6