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Shared and Distinct Phenotypes and Functions of Human CD161++ V alpha 7.2+T Cell Subsets
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Number of Authors: 10
2017 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, 1031Article in journal (Refereed) Published
Abstract [en]

Human mucosal-associated invariant T (MAIT) cells are an important T cell subset that are enriched in tissues and possess potent effector functions. Typically such cells are marked by their expression of V alpha 7.2-J alpha 33/J alpha 20/J alpha 12 T cell receptors, and functionally they are major histocompatibility complex class I-related protein 1 (MR1)-restricted, responding to bacterially derived riboflavin synthesis intermediates. MAIT cells are contained within the CD161++ V alpha 7.2+ T cell population, the majority of which express the CD8 receptor (CD8+), while a smaller fraction expresses neither CD8 or CD4 coreceptor (double negative; DN) and a further minority are CD4+. Whether these cells have distinct homing patterns, phenotype and functions have not been examined in detail. We used a combination of phenotypic staining and functional assays to address the similarities and differences between these CD161++ V alpha 7.2+ T cell subsets. We find that most features are shared between CD8+ and DN CD161++ V alpha 7.2+ T cells, with a small but detectable role evident for CD8 binding in tuning functional responsiveness. By contrast, the CD4+ CD161++ V alpha 7.2+ T cell population, although showing MR1-dependent responsiveness to bacterial stimuli, display reduced T helper 1 effector functions, including cytolytic machinery, while retaining the capacity to secrete interleukin-4 (IL-4) and IL-13. This was consistent with underlying changes in transcription factor (TF) expression. Although we found that only a proportion of CD4+ CD161++ V alpha 7.2+ T cells stained for the MR1-tetramer, explaining some of the heterogeneity of CD4+ CD161++ V alpha 7.2+ T cells, these differences in TF expression were shared with CD4+ CD161++ MR1-tetramer+ cells. These data reveal the functional diversity of human CD161++ V alpha 7.2+ T cells and indicate potentially distinct roles for the different subsets in vivo.

Place, publisher, year, edition, pages
2017. Vol. 8, 1031
Keyword [en]
mucosal-associated invariant T cells, innate-like T cells, MHC class I-related protein 1-tetramer, MHC class I-related protein 1, subsets, transcription factors, CD8 coreceptor
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:su:diva-147047DOI: 10.3389/fimmu.2017.01031ISI: 000409049500001OAI: oai:DiVA.org:su-147047DiVA: diva2:1143058
Available from: 2017-09-20 Created: 2017-09-20 Last updated: 2017-09-20Bibliographically approved

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Sverremark-Ekström, Eva
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Department of Molecular Biosciences, The Wenner-Gren Institute
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