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Minor H Antigen HA-1–specific Regulator and Effector CD8(+) T Cells, and HA-1 Microchimerism, in Allograft Tolerance

The role of the hematopoietic lineage-restricted minor histocompatibility (H) antigen HA-1 in renal allograft tolerance was explored. We obtained peripheral blood samples from three recipients of histocompatibility leukocyte antigen (HLA)–matched, HA-1–mismatched renal transplants, one of which had...

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Autores principales: Cai, Junchao, Lee, Junglim, Jankowska-Gan, Ewa, Derks, Richard, Pool, Jos, Mutis, Tuna, Goulmy, Els, Burlingham, William J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211880/
https://www.ncbi.nlm.nih.gov/pubmed/15067036
http://dx.doi.org/10.1084/jem.20031012
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author Cai, Junchao
Lee, Junglim
Jankowska-Gan, Ewa
Derks, Richard
Pool, Jos
Mutis, Tuna
Goulmy, Els
Burlingham, William J.
author_facet Cai, Junchao
Lee, Junglim
Jankowska-Gan, Ewa
Derks, Richard
Pool, Jos
Mutis, Tuna
Goulmy, Els
Burlingham, William J.
author_sort Cai, Junchao
collection PubMed
description The role of the hematopoietic lineage-restricted minor histocompatibility (H) antigen HA-1 in renal allograft tolerance was explored. We obtained peripheral blood samples from three recipients of histocompatibility leukocyte antigen (HLA)–matched, HA-1–mismatched renal transplants, one of which had discontinued immunosuppression >30 yr ago while sustaining normal kidney function. Peripheral blood mononuclear cells (PBMCs) were injected into the footpads of severe combined immunodeficiency mice to measure human delayed type hypersensitivity (DTH) responses. All three patients manifested regulated DTH responses to HA-1(H) peptide. By differential tetramer staining intensities, we observed two distinct minor H antigen HA-1–specific CD8(+) T cell subsets. The one that stained dimly had the characteristics of a T regulatory (T(R)) cell and produced interleukin (IL) 10 and/or transforming growth factor (TGF) β. These HA-1–specific T(R) cells coexisted with bright tetramer-binding CD8(+) T effector (T(E)) cells. The CD8(+) T(E) cells mediated HA-1–specific DTH and produced interferon-γ. Suppression of these T(E) functions by T(R) cells was TGFβ, IL-10, and cytotoxic T lymphocyte–associated antigen 4 dependent. In addition, HA-1 microchimerism was detected in two recipients, primarily in the dendritic cell fraction of the PBMCs. This is the first demonstration of coexisting CD8(+) memory T(R) and T(E) cells, both specific for the same HA-1 antigen, in the context of renal allograft tolerance.
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spelling pubmed-22118802008-03-11 Minor H Antigen HA-1–specific Regulator and Effector CD8(+) T Cells, and HA-1 Microchimerism, in Allograft Tolerance Cai, Junchao Lee, Junglim Jankowska-Gan, Ewa Derks, Richard Pool, Jos Mutis, Tuna Goulmy, Els Burlingham, William J. J Exp Med Brief Definitive Report The role of the hematopoietic lineage-restricted minor histocompatibility (H) antigen HA-1 in renal allograft tolerance was explored. We obtained peripheral blood samples from three recipients of histocompatibility leukocyte antigen (HLA)–matched, HA-1–mismatched renal transplants, one of which had discontinued immunosuppression >30 yr ago while sustaining normal kidney function. Peripheral blood mononuclear cells (PBMCs) were injected into the footpads of severe combined immunodeficiency mice to measure human delayed type hypersensitivity (DTH) responses. All three patients manifested regulated DTH responses to HA-1(H) peptide. By differential tetramer staining intensities, we observed two distinct minor H antigen HA-1–specific CD8(+) T cell subsets. The one that stained dimly had the characteristics of a T regulatory (T(R)) cell and produced interleukin (IL) 10 and/or transforming growth factor (TGF) β. These HA-1–specific T(R) cells coexisted with bright tetramer-binding CD8(+) T effector (T(E)) cells. The CD8(+) T(E) cells mediated HA-1–specific DTH and produced interferon-γ. Suppression of these T(E) functions by T(R) cells was TGFβ, IL-10, and cytotoxic T lymphocyte–associated antigen 4 dependent. In addition, HA-1 microchimerism was detected in two recipients, primarily in the dendritic cell fraction of the PBMCs. This is the first demonstration of coexisting CD8(+) memory T(R) and T(E) cells, both specific for the same HA-1 antigen, in the context of renal allograft tolerance. The Rockefeller University Press 2004-04-05 /pmc/articles/PMC2211880/ /pubmed/15067036 http://dx.doi.org/10.1084/jem.20031012 Text en Copyright © 2004, 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 Brief Definitive Report
Cai, Junchao
Lee, Junglim
Jankowska-Gan, Ewa
Derks, Richard
Pool, Jos
Mutis, Tuna
Goulmy, Els
Burlingham, William J.
Minor H Antigen HA-1–specific Regulator and Effector CD8(+) T Cells, and HA-1 Microchimerism, in Allograft Tolerance
title Minor H Antigen HA-1–specific Regulator and Effector CD8(+) T Cells, and HA-1 Microchimerism, in Allograft Tolerance
title_full Minor H Antigen HA-1–specific Regulator and Effector CD8(+) T Cells, and HA-1 Microchimerism, in Allograft Tolerance
title_fullStr Minor H Antigen HA-1–specific Regulator and Effector CD8(+) T Cells, and HA-1 Microchimerism, in Allograft Tolerance
title_full_unstemmed Minor H Antigen HA-1–specific Regulator and Effector CD8(+) T Cells, and HA-1 Microchimerism, in Allograft Tolerance
title_short Minor H Antigen HA-1–specific Regulator and Effector CD8(+) T Cells, and HA-1 Microchimerism, in Allograft Tolerance
title_sort minor h antigen ha-1–specific regulator and effector cd8(+) t cells, and ha-1 microchimerism, in allograft tolerance
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211880/
https://www.ncbi.nlm.nih.gov/pubmed/15067036
http://dx.doi.org/10.1084/jem.20031012
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