Elevated expression of LAG-3, but not PD-1, is associated with impaired iNKT cytokine production during chronic HIV-1 infection and treatment
| Autor: | Joshua Kimani, Jillian L.M. Waruk, Makobu Kimani, Keith R. Fowke, Jennifer A Juno, Julius Oyugi, Francis A. Plummer, Andrew T. Stalker |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Adult
Chemokine Exhaustion medicine.medical_treatment Programmed Cell Death 1 Receptor Gene Expression HIV Infections Cohort Studies Immune system Antigen Downregulation and upregulation Antigens CD Virology medicine Humans Interferon gamma iNKT cells Sex Workers biology Research HIV Middle Aged Natural killer T cell Kenya Lymphocyte Activation Gene 3 Protein Healthy Volunteers 3. Good health Up-Regulation Cytokine Infectious Diseases CD223 Immune dysfunction Immunology Host-Pathogen Interactions biology.protein HIV-1 Cytokines Natural Killer T-Cells Female Antibody LAG-3 protein human medicine.drug |
| Zdroj: | Retrovirology |
| ISSN: | 1742-4690 |
| DOI: | 10.1186/s12977-015-0142-z |
| Popis: | Background LAG-3 is a potent negative regulator of the immune response but its impact in HIV infection in poorly understood. Unlike exhaustion markers such as PD-1, Tim-3, 2B4 and CD160, LAG-3 is poorly expressed on bulk and antigen-specific T cells during chronic HIV infection and its expression on innate lymphocyte subsets is not well understood. The aim of this study was to assess LAG-3 expression and association with cellular dysfunction on T cells, NK cells and iNKT cells among a cohort of healthy and HIV-infected female sex workers in Nairobi, Kenya. Results Ex vivo LAG-3 expression was measured by multiparametric flow cytometry, and plasma cytokine/chemokine concentrations measured by bead array. Although LAG-3 expression on bulk T cells was significantly increased among HIV-infected women, the proportion of cells expressing the marker was extremely low. In contrast, LAG-3 was more highly expressed on NK and iNKT cells and was not reduced among women treated with ART. To assess the functional impact of LAG-3 on iNKT cells, iNKT cytokine production was measured in response to lipid (αGalCer) and PMA/Io stimulation by both flow cytometry and cytokine bead array. iNKT cytokine production is profoundly altered by both HIV infection and treatment, and LAG-3, but not PD-1, expression is associated with a reduction in iNKT IFNγ production. Conclusions LAG-3 does not appear to mediate T cell exhaustion in this African population, but is instead expressed on innate lymphocyte subsets including iNKT cells. HIV infection alters iNKT cytokine production patterns and LAG-3 expression is uniquely associated with iNKT dysfunction. The continued expression of LAG-3 during treatment suggests it may contribute to the lack of innate immune reconstitution commonly observed during ART. Electronic supplementary material The online version of this article (doi:10.1186/s12977-015-0142-z) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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