Attrition of TCR Vα7.2+ CD161++ MAIT Cells in HIV-Tuberculosis Co-Infection Is Associated with Elevated Levels of PD-1 Expression
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,...
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Published in | PloS one Vol. 10; no. 4; p. e0124659 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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20.04.2015
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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. |
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AbstractList | 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. 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. |
Author | Velu, Vijayakumar Ansari, Abdul W. Rukumani, Devi V. Al-Batran, Rami Shankar, Esaki M. Tan, Hong Y. Barathan, Muttiah Larsson, Marie Al-Darraji, Haider A. Ponnampalavanar, Sasheela Kamarulzaman, Adeeba Saeidi, Alireza Yong, Yean K. Tien Tien, Vicky L. |
AuthorAffiliation | 5 Department of Microbiology and Immunology, Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA 30329, United States of America 1 Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia 6 Molekylär Virologi, Institutionen för Klinisk Och Experimentell Medicin, Linköpings Universitet, 581 85 Linköping, Sweden 3 Department of Biomedical Science, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia 2 Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia Karolinska Institutet, SWEDEN 4 Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia |
AuthorAffiliation_xml | – name: 5 Department of Microbiology and Immunology, Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA 30329, United States of America – name: 1 Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia – name: 4 Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia – name: 3 Department of Biomedical Science, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia – name: 2 Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia – name: 6 Molekylär Virologi, Institutionen för Klinisk Och Experimentell Medicin, Linköpings Universitet, 581 85 Linköping, Sweden – name: Karolinska Institutet, SWEDEN |
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Copyright | 2015 Saeidi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2015 Saeidi et al 2015 Saeidi et al |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: AS VL MB EMS. Performed the experiments: AS VL MB EMS. Analyzed the data: AS VL RA EMS. Contributed reagents/materials/analysis tools: HAA SP VDR HYT YYK AWA AK EMS. Wrote the paper: VV AK ML EMS. AS VL VV ML EMS. |
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Snippet | Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8(+) T cells co-expressing the semi-invariant TCR... Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8+ T cells co-expressing the semi-invariant TCR Vα7.2,... Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8 + T cells co-expressing the semi-invariant TCR Vα7.2,... |
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SubjectTerms | Acquired immune deficiency syndrome Adult AIDS Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Antitubercular Agents - pharmacology Antitubercular Agents - therapeutic use CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - metabolism Cell Count Coinfection - drug therapy Coinfection - immunology Cross-Sectional Studies Exhaustion Female Flow cytometry Gene Expression Regulation - drug effects HIV HIV Infections - drug therapy HIV Infections - immunology Human immunodeficiency virus Humans Immune response Infections Invariants Lymphocytes Male NK Cell Lectin-Like Receptor Subfamily B - metabolism Patients Phenotype Programmed Cell Death 1 Receptor - metabolism Receptors, Antigen, T-Cell - metabolism Receptors, CCR6 - metabolism T cell receptors Therapy Tuberculosis Tuberculosis - drug therapy Tuberculosis - immunology Viruses |
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Title | Attrition of TCR Vα7.2+ CD161++ MAIT Cells in HIV-Tuberculosis Co-Infection Is Associated with Elevated Levels of PD-1 Expression |
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