Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.

The monoclonal anti-CD20 antibody rituximab (RTX) depletes B cells in the treatment of lymphoma and autoimmune disease, and contributes to alloantibody reduction in transplantation across immunologic barriers. The effects of RTX on T cells are less well described. T-follicular helper (Tfh) cells pro...

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Main Authors: Wallin, E, Jolly, E, Suchánek, O, Bradley, J, Espéli, M, Jayne, DR, Linterman, M, Smith, K
Format: Journal article
Language:English
Published: 2014
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author Wallin, E
Jolly, E
Suchánek, O
Bradley, J
Espéli, M
Jayne, DR
Linterman, M
Smith, K
author_facet Wallin, E
Jolly, E
Suchánek, O
Bradley, J
Espéli, M
Jayne, DR
Linterman, M
Smith, K
author_sort Wallin, E
collection OXFORD
description The monoclonal anti-CD20 antibody rituximab (RTX) depletes B cells in the treatment of lymphoma and autoimmune disease, and contributes to alloantibody reduction in transplantation across immunologic barriers. The effects of RTX on T cells are less well described. T-follicular helper (Tfh) cells provide growth and differentiation signals to germinal center (GC) B cells to support antibody production, and suppressive T-follicular regulatory (Tfr) cells regulate this response. In mice, both Tfh and Tfr are absolutely dependent on B cells for their formation and on the GC for their maintenance. In this study, we demonstrate that RTX treatment results in a lack of GC B cells in human lymph nodes without affecting the Tfh or Tfr cell populations. These data demonstrate that human Tfh and Tfr do not require an ongoing GC response for their maintenance. The persistence of Tfh and Tfr following RTX treatment may permit rapid reconstitution of the pathological GC response once the B-cell pool begins to recover. Strategies for maintaining remission after RTX therapy will need to take this persistence of Tfh into account.
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spelling oxford-uuid:3d0c760c-8844-41ae-a4d5-e11b0c81bce92022-03-26T14:17:18ZHuman T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3d0c760c-8844-41ae-a4d5-e11b0c81bce9EnglishSymplectic Elements at Oxford2014Wallin, EJolly, ESuchánek, OBradley, JEspéli, MJayne, DRLinterman, MSmith, KThe monoclonal anti-CD20 antibody rituximab (RTX) depletes B cells in the treatment of lymphoma and autoimmune disease, and contributes to alloantibody reduction in transplantation across immunologic barriers. The effects of RTX on T cells are less well described. T-follicular helper (Tfh) cells provide growth and differentiation signals to germinal center (GC) B cells to support antibody production, and suppressive T-follicular regulatory (Tfr) cells regulate this response. In mice, both Tfh and Tfr are absolutely dependent on B cells for their formation and on the GC for their maintenance. In this study, we demonstrate that RTX treatment results in a lack of GC B cells in human lymph nodes without affecting the Tfh or Tfr cell populations. These data demonstrate that human Tfh and Tfr do not require an ongoing GC response for their maintenance. The persistence of Tfh and Tfr following RTX treatment may permit rapid reconstitution of the pathological GC response once the B-cell pool begins to recover. Strategies for maintaining remission after RTX therapy will need to take this persistence of Tfh into account.
spellingShingle Wallin, E
Jolly, E
Suchánek, O
Bradley, J
Espéli, M
Jayne, DR
Linterman, M
Smith, K
Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.
title Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.
title_full Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.
title_fullStr Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.
title_full_unstemmed Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.
title_short Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.
title_sort human t follicular helper and t follicular regulatory cell maintenance is independent of germinal centers
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