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An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells

The effects of a chimeric monoclonal antibody (chA6 mAb) that recognizes both the RO and RB isoforms of the transmembrane protein tyrosine phosphatase CD45 on human T cells were investigated. Chimeric A6 (chA6) mAb potently inhibited antigen-specific and polyclonal T cell responses. ChA6 mAb induced...

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Autores principales: Gregori, Silvia, Mangia, Patrizia, Bacchetta, Rosa, Tresoldi, Eleonora, Kolbinger, Frank, Traversari, Catia, Carballido, Josè M., de Vries, Jan E., Korthäuer, Ulf, Roncarolo, Maria-Grazia
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213149/
https://www.ncbi.nlm.nih.gov/pubmed/15837814
http://dx.doi.org/10.1084/jem.20040912
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author Gregori, Silvia
Mangia, Patrizia
Bacchetta, Rosa
Tresoldi, Eleonora
Kolbinger, Frank
Traversari, Catia
Carballido, Josè M.
de Vries, Jan E.
Korthäuer, Ulf
Roncarolo, Maria-Grazia
author_facet Gregori, Silvia
Mangia, Patrizia
Bacchetta, Rosa
Tresoldi, Eleonora
Kolbinger, Frank
Traversari, Catia
Carballido, Josè M.
de Vries, Jan E.
Korthäuer, Ulf
Roncarolo, Maria-Grazia
author_sort Gregori, Silvia
collection PubMed
description The effects of a chimeric monoclonal antibody (chA6 mAb) that recognizes both the RO and RB isoforms of the transmembrane protein tyrosine phosphatase CD45 on human T cells were investigated. Chimeric A6 (chA6) mAb potently inhibited antigen-specific and polyclonal T cell responses. ChA6 mAb induced activation-independent apoptosis in CD4(+)CD45RO/RB(high) T cells but not in CD8(+) T cells. In addition, CD4(+) T cell lines specific for tetanus toxoid (TT) generated in the presence of chA6 mAb were anergic and suppressed the proliferation and interferon (IFN)-γ production by TT-specific effector T cells by an interleukin-10–dependent mechanism, indicating that these cells were equivalent to type 1 regulatory T cells. Similarly, CD8(+) T cell lines specific for the influenza A matrix protein-derived peptide (MP.58-66) generated in the presence of chA6 mAb were anergic and suppressed IFN-γ production by MP.58-66–specific effector CD8(+) T cells. Furthermore, chA6 mAb significantly prolonged human pancreatic islet allograft survival in nonobese diabetic/severe combined immunodeficiency mice injected with human peripheral blood lymphocytes (hu-PBL-NOD/SCID). Together, these results demonstrate that the chA6 mAb is a new immunomodulatory agent with multiple modes of action, including deletion of preexisting memory and recently activated T cells and induction of anergic CD4(+) and CD8(+) regulatory T cells.
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spelling pubmed-22131492008-03-11 An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells Gregori, Silvia Mangia, Patrizia Bacchetta, Rosa Tresoldi, Eleonora Kolbinger, Frank Traversari, Catia Carballido, Josè M. de Vries, Jan E. Korthäuer, Ulf Roncarolo, Maria-Grazia J Exp Med Article The effects of a chimeric monoclonal antibody (chA6 mAb) that recognizes both the RO and RB isoforms of the transmembrane protein tyrosine phosphatase CD45 on human T cells were investigated. Chimeric A6 (chA6) mAb potently inhibited antigen-specific and polyclonal T cell responses. ChA6 mAb induced activation-independent apoptosis in CD4(+)CD45RO/RB(high) T cells but not in CD8(+) T cells. In addition, CD4(+) T cell lines specific for tetanus toxoid (TT) generated in the presence of chA6 mAb were anergic and suppressed the proliferation and interferon (IFN)-γ production by TT-specific effector T cells by an interleukin-10–dependent mechanism, indicating that these cells were equivalent to type 1 regulatory T cells. Similarly, CD8(+) T cell lines specific for the influenza A matrix protein-derived peptide (MP.58-66) generated in the presence of chA6 mAb were anergic and suppressed IFN-γ production by MP.58-66–specific effector CD8(+) T cells. Furthermore, chA6 mAb significantly prolonged human pancreatic islet allograft survival in nonobese diabetic/severe combined immunodeficiency mice injected with human peripheral blood lymphocytes (hu-PBL-NOD/SCID). Together, these results demonstrate that the chA6 mAb is a new immunomodulatory agent with multiple modes of action, including deletion of preexisting memory and recently activated T cells and induction of anergic CD4(+) and CD8(+) regulatory T cells. The Rockefeller University Press 2005-04-18 /pmc/articles/PMC2213149/ /pubmed/15837814 http://dx.doi.org/10.1084/jem.20040912 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Gregori, Silvia
Mangia, Patrizia
Bacchetta, Rosa
Tresoldi, Eleonora
Kolbinger, Frank
Traversari, Catia
Carballido, Josè M.
de Vries, Jan E.
Korthäuer, Ulf
Roncarolo, Maria-Grazia
An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells
title An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells
title_full An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells
title_fullStr An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells
title_full_unstemmed An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells
title_short An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells
title_sort anti-cd45ro/rb monoclonal antibody modulates t cell responses via induction of apoptosis and generation of regulatory t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213149/
https://www.ncbi.nlm.nih.gov/pubmed/15837814
http://dx.doi.org/10.1084/jem.20040912
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