CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4+ T Cells
Background: Mucosa-associated invariant T (MAIT) cells are a recently identified class of innate-like T cells that are involved in the mucosal immune response. MAIT cells are characterized by expression of TCR Va7.2 and CD161. In HIV infection, there is a profound early loss of MAIT cells from the c...
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| Format: | Article |
| Language: | English |
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Case Western Reserve University
2017-08-01
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| Series: | Pathogens and Immunity |
| Subjects: | |
| Online Access: | http://paijournal.com/index.php/paijournal/article/view/136 |
| _version_ | 1818137420242092032 |
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| author | Michael L Freeman Stephen R. Morris Michael M. Lederman |
| author_facet | Michael L Freeman Stephen R. Morris Michael M. Lederman |
| author_sort | Michael L Freeman |
| collection | DOAJ |
| description | Background: Mucosa-associated invariant T (MAIT) cells are a recently identified class of innate-like T cells that are involved in the mucosal immune response. MAIT cells are characterized by expression of TCR Va7.2 and CD161. In HIV infection, there is a profound early loss of MAIT cells from the circulation that never fully recovers, even after prolonged viral control with antiretroviral therapy (ART).
Methods: We analyzed PBMCs from fresh whole blood from HIV-negative or ART-treated HIV-positive donors with full (Immune Success) or impaired (Immune Failure) CD4+ T- cell recovery by flow cytometry for T-cell markers, TCR Va7.2, and CD161. The PBMCs were cultured with or without TCR-mediated stimulation, and CD161 expression was assessed on Va7.2+ T cells. Interferon-g (IFNg) production was assessed by intracellular cytokine staining.
Results: We found a decrease in the percentage of CD3+ T cells that expressed CD161 and the percentage of Va7.2+ T cells that expressed CD161, in HIV-infected individuals. We also found a significant increase in the percentage of T cells that were Va7.2+CD161- in immune failure compared to controls, accompanied by an increase in the percentage of Va7.2+CD161- T cells that express CD8+ in donors with immune failure, but not immune success. After TCR stimulation in vitro, Va7.2+ T cells reduced expression of CD161, yet Va7.2+ CD161- cells from immune failure donors retained the ability to express IFNg on stimulation.
Conclusions: Our findings suggest that in immune failure patients, the reduction in peripheral MAIT cells is due, at least in part, to a loss in CD161 expression, and is not merely the result of trafficking into mucosal tissues or cell death. These CD161- cells retain their function. |
| first_indexed | 2024-12-11T09:56:01Z |
| format | Article |
| id | doaj.art-a838ec877eed4fed8cc611f4d5ebc9f5 |
| institution | Directory Open Access Journal |
| issn | 2469-2964 |
| language | English |
| last_indexed | 2024-12-11T09:56:01Z |
| publishDate | 2017-08-01 |
| publisher | Case Western Reserve University |
| record_format | Article |
| series | Pathogens and Immunity |
| spelling | doaj.art-a838ec877eed4fed8cc611f4d5ebc9f52022-12-22T01:12:16ZengCase Western Reserve UniversityPathogens and Immunity2469-29642017-08-012333535110.20411/pai.v2i3.13666CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4+ T CellsMichael L Freeman0Stephen R. Morris1Michael M. Lederman2Case Western Reserve UniversityLouis Stokes Cleveland VA Medical Center, Cleveland, OhioCenter for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OhioBackground: Mucosa-associated invariant T (MAIT) cells are a recently identified class of innate-like T cells that are involved in the mucosal immune response. MAIT cells are characterized by expression of TCR Va7.2 and CD161. In HIV infection, there is a profound early loss of MAIT cells from the circulation that never fully recovers, even after prolonged viral control with antiretroviral therapy (ART). Methods: We analyzed PBMCs from fresh whole blood from HIV-negative or ART-treated HIV-positive donors with full (Immune Success) or impaired (Immune Failure) CD4+ T- cell recovery by flow cytometry for T-cell markers, TCR Va7.2, and CD161. The PBMCs were cultured with or without TCR-mediated stimulation, and CD161 expression was assessed on Va7.2+ T cells. Interferon-g (IFNg) production was assessed by intracellular cytokine staining. Results: We found a decrease in the percentage of CD3+ T cells that expressed CD161 and the percentage of Va7.2+ T cells that expressed CD161, in HIV-infected individuals. We also found a significant increase in the percentage of T cells that were Va7.2+CD161- in immune failure compared to controls, accompanied by an increase in the percentage of Va7.2+CD161- T cells that express CD8+ in donors with immune failure, but not immune success. After TCR stimulation in vitro, Va7.2+ T cells reduced expression of CD161, yet Va7.2+ CD161- cells from immune failure donors retained the ability to express IFNg on stimulation. Conclusions: Our findings suggest that in immune failure patients, the reduction in peripheral MAIT cells is due, at least in part, to a loss in CD161 expression, and is not merely the result of trafficking into mucosal tissues or cell death. These CD161- cells retain their function.http://paijournal.com/index.php/paijournal/article/view/136HIVImmune FailureMAIT cells |
| spellingShingle | Michael L Freeman Stephen R. Morris Michael M. Lederman CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4+ T Cells Pathogens and Immunity HIV Immune Failure MAIT cells |
| title | CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4+ T Cells |
| title_full | CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4+ T Cells |
| title_fullStr | CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4+ T Cells |
| title_full_unstemmed | CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4+ T Cells |
| title_short | CD161 Expression on Mucosa-Associated Invariant T Cells is Reduced in HIV-Infected Subjects Undergoing Antiretroviral Therapy Who Do Not Recover CD4+ T Cells |
| title_sort | cd161 expression on mucosa associated invariant t cells is reduced in hiv infected subjects undergoing antiretroviral therapy who do not recover cd4 t cells |
| topic | HIV Immune Failure MAIT cells |
| url | http://paijournal.com/index.php/paijournal/article/view/136 |
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