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Shared and Distinct Phenotypes and Functions of Human CD161++ Vα7.2+ T Cell Subsets

Lookup NU author(s): Dr Lucy Walker

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2017 Kurioka, Jahun, Hannaway, Walker, Fergusson, Sverremark-Ekström, Corbett, Ussher, Willberg and Klenerman. 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 Vα7.2-Jα33/Jα20/Jα12 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++ Vα7.2+ 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++ Vα7.2+ T cell subsets. We find that most features are shared between CD8+ and DN CD161++ Vα7.2+ T cells, with a small but detectable role evident for CD8 binding in tuning functional responsiveness. By contrast, the CD4+ CD161++ Vα7.2+ 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++ Vα7.2+ T cells stained for the MR1-tetramer, explaining some of the heterogeneity of CD4+ CD161++ Vα7.2+ T cells, these differences in TF expression were shared with CD4+ CD161++ MR1-tetramer+ cells. These data reveal the functional diversity of human CD161++ Vα7.2+ T cells and indicate potentially distinct roles for the different subsets in vivo.

Publication metadata

Author(s): Kurioka A, Jahun AS, Hannaway RF, Walker LJ, Fergusson JR, Sverremark-Ekstrom E, Corbett AJ, Ussher JE, Willberg CB, Klenerman P

Publication type: Article

Publication status: Published

Journal: Frontiers in Immunology

Year: 2017

Volume: 8

Online publication date: 30/08/2017

Acceptance date: 09/08/2017

Date deposited: 24/10/2017

ISSN (electronic): 1664-3224

Publisher: Frontiers Media S.A.

URL: https://doi.org/10.3389/fimmu.2017.01031

DOI: 10.3389/fimmu.2017.01031

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