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 inPloS one Vol. 10; no. 4; p. e0124659
Main Authors Saeidi, Alireza, Tien Tien, Vicky L., Al-Batran, Rami, Al-Darraji, Haider A., Tan, Hong Y., Yong, Yean K., Ponnampalavanar, Sasheela, Barathan, Muttiah, Rukumani, Devi V., Ansari, Abdul W., Velu, Vijayakumar, Kamarulzaman, Adeeba, Larsson, Marie, Shankar, Esaki M.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 20.04.2015
Public Library of Science (PLoS)
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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.
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
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/25894562$$D View this record in MEDLINE/PubMed
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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
Copyright_xml – notice: 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.
– notice: 2015 Saeidi et al 2015 Saeidi et al
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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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