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Int. J. Mol. Sci. 2017, 18(7), 1603; doi:10.3390/ijms18071603

Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation

1
Department of Clinical Immunology, Aalborg University Hospital, Urbansgade 32-36, DK-9000 Aalborg, Denmark
2
Department of Health Science and Technology, Aalborg University, Laboratory for Medical Mass Spectrometry, Fredrik Bajersvej 7E, 9100 Aalborg, Denmark
*
Author to whom correspondence should be addressed.
Received: 14 June 2017 / Revised: 14 July 2017 / Accepted: 19 July 2017 / Published: 24 July 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Although the observation of major histocompatibility complex II (MHCII) receptors on T cells is longstanding, the explanation for this occurrence remains enigmatic. Reports of an inducible, endogenous expression exist, as do studies demonstrating a protein acquisition from other cells by mechanisms including vesicle transfer. Irrespective of origin, the presence of the human MHCII isotype, human leukocyte antigen DR (HLA-DR), potentially identifies a regulatory T cell population. Using an allogeneic mixed lymphocyte culture (MLC) to induce an antigen-specific immune response, the role of antigen-presenting cells (APCs) for the presence of HLA-DR on cluster of differentiation 3(CD3)+ CD4+ T cells was evaluated. Moreover, a functional phenotype was established for these T cells. It was demonstrated that APCs were essential for HLA-DR on CD3+ CD4+ T cells. Additionally, a regulatory T cell phenotype was induced in CD3+ CD4+ HLA-DR+ responder T cells with an expression of CD25, CTLA-4, CD62L, PD-1, and TNFRII. This phenotype was induced both with and without physical T cell:APC contact, which could reveal novel indications about its functionality. To further investigate contact-independent communication, a phenotype of the small cell-derived vesicles from the MLCs was determined. Yet heterogeneous, this vesicle phenotype displayed contact-dependent differences, providing clues about their intended function in cellular communication. View Full-Text
Keywords: peripheral tolerance; regulatory T cells; flow cytometry; EV Array peripheral tolerance; regulatory T cells; flow cytometry; EV Array
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Revenfeld, A.L.S.; Bæk, R.; Jørgensen, M.M.; Varming, K.; Stensballe, A. Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation. Int. J. Mol. Sci. 2017, 18, 1603.

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