Characterization of human T follicular regulatory cells

Characterization of human T follicular regulatory cells

Bibliographic Details
Main Author: Sayin, Ismail
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2019
Subjects:
Biology
Immunology
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1560336991188191
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case15603369911881912021-08-03T07:11:21Z Characterization of human T follicular regulatory cells Sayin, Ismail Biology Immunology Germinal centers (GC) are temporary structures that arise in B cell follicles in secondary lymphoid organs in response to T cell-dependent antigen. Within these well-organized GC structures, T follicular helper (Tfh) cells, a novel subset of CD4 T cells, help B cells differentiate into high-affinity antibody-producing plasma cells and memory B cells which can respond rapidly in case of re-exposure. Tfh-B cell interaction is crucial for an effective antibody response and is required to be strictly regulated in order to prevent autoimmune diseases and uncontrolled expansion of Tfh and B cells. Tfh-B regulation has been mainly performed by T follicular regulatory (Tfr) cells, a recently identified T regulatory (Treg) cell subset. Here, we characterized human Tfr cells isolated from mesenteric lymph nodes (mLN). We observed that Tfr cells most reside in the T cell zone - B cell follicle border and very few reside within GC. We also showed that human Tfr cells express less Programmed cell death 1 (PD-1) compared to murine counterparts. Both the PD-1 positive and PD-1 negative Tfr cells efficiently suppress Tfh cell-mediated B cell IgG and IgA production. We also showed that Tfr cells transcriptionally are more similar to Treg cells than Tfh cells. These findings show us that Tfr cells are very potent suppressors and function mostly in T-B border and within B cell follicle not in GC.Even though Tfr cells were well characterized, how they suppress Tfh-mediated B cell antibody production is still unknown. Here, to understand the mechanism, we conduct Tfh cell –Tfr cell – B cell coculture experiments. We observe that Tfr cells suppress Tfh cell and B cell proliferation and activation. Tfr cells also inhibit the expression of costimulatory receptors on Tfh cells and B cells. These data are the first step to understand the human Tfr cell suppression mechanism by understanding the changes in Tfh cells and B cells in the presence of Tfr cells. 2019-08-28 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1560336991188191 http://rave.ohiolink.edu/etdc/view?acc_num=case1560336991188191 unrestricted This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.
collection NDLTD
language English
sources NDLTD
topic Biology
Immunology
spellingShingle Biology
Immunology
Sayin, Ismail
Characterization of human T follicular regulatory cells
author Sayin, Ismail
author_facet Sayin, Ismail
author_sort Sayin, Ismail
title Characterization of human T follicular regulatory cells
title_short Characterization of human T follicular regulatory cells
title_full Characterization of human T follicular regulatory cells
title_fullStr Characterization of human T follicular regulatory cells
title_full_unstemmed Characterization of human T follicular regulatory cells
title_sort characterization of human t follicular regulatory cells
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2019
url http://rave.ohiolink.edu/etdc/view?acc_num=case1560336991188191
work_keys_str_mv AT sayinismail characterizationofhumantfollicularregulatorycells
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