Development of graft-vs-host disease-like syndrome in cyclosporine-treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity

A. D. Hess, L. Horwitz, W. E. Beschorner, G. W. Santos

Research output: Contribution to journalArticle

Abstract

Lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporine (CsA) for 40 d develop a graft-vs-host disease-like syndrome (GVHD) after CsA therapy. We attempted to assess the development of auto-reactivity in these animals. Results revealed that a majority of the animals with syngeneic GVHD develop autocytotoxic T lymphocytes of the OX8 phenotype. In addition to reactivity with self, these cells were capable of lysing appropriate target cells from a variety of different rat strains. The target antigens appeared to be class II major histocompatibility antigens, because lysis could be effectively blocked by an anti-Ia monoclonal antibody. Cold target inhibition studies indicated that one effector-cell was capable of lysing various target cells, and provided evidence against a polyclonal activation of multiple anti-Ia-reactive cells. These results suggested that the anti-class II autoreactive cell-associated with syngeneic GVHD either recognizes a common class II determinant ('public ' epitope) shared by multiple strains of rats, or was polyspecific with respect to 'private' class II determinants.

Original languageEnglish (US)
Pages (from-to)718-730
Number of pages13
JournalJournal of Experimental Medicine
Volume161
Issue number4
StatePublished - 1985

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Isogeneic Transplantation
Cytotoxic T-Lymphocytes
Graft vs Host Disease
Bone Marrow Transplantation
Cyclosporine
Histocompatibility Antigens Class II
Epitopes
Bone Marrow
Monoclonal Antibodies
T-Lymphocytes
Phenotype
Antigens

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Development of graft-vs-host disease-like syndrome in cyclosporine-treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity",
abstract = "Lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporine (CsA) for 40 d develop a graft-vs-host disease-like syndrome (GVHD) after CsA therapy. We attempted to assess the development of auto-reactivity in these animals. Results revealed that a majority of the animals with syngeneic GVHD develop autocytotoxic T lymphocytes of the OX8 phenotype. In addition to reactivity with self, these cells were capable of lysing appropriate target cells from a variety of different rat strains. The target antigens appeared to be class II major histocompatibility antigens, because lysis could be effectively blocked by an anti-Ia monoclonal antibody. Cold target inhibition studies indicated that one effector-cell was capable of lysing various target cells, and provided evidence against a polyclonal activation of multiple anti-Ia-reactive cells. These results suggested that the anti-class II autoreactive cell-associated with syngeneic GVHD either recognizes a common class II determinant ('public ' epitope) shared by multiple strains of rats, or was polyspecific with respect to 'private' class II determinants.",
author = "Hess, {A. D.} and L. Horwitz and Beschorner, {W. E.} and Santos, {G. W.}",
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AU - Hess, A. D.

AU - Horwitz, L.

AU - Beschorner, W. E.

AU - Santos, G. W.

PY - 1985

Y1 - 1985

N2 - Lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporine (CsA) for 40 d develop a graft-vs-host disease-like syndrome (GVHD) after CsA therapy. We attempted to assess the development of auto-reactivity in these animals. Results revealed that a majority of the animals with syngeneic GVHD develop autocytotoxic T lymphocytes of the OX8 phenotype. In addition to reactivity with self, these cells were capable of lysing appropriate target cells from a variety of different rat strains. The target antigens appeared to be class II major histocompatibility antigens, because lysis could be effectively blocked by an anti-Ia monoclonal antibody. Cold target inhibition studies indicated that one effector-cell was capable of lysing various target cells, and provided evidence against a polyclonal activation of multiple anti-Ia-reactive cells. These results suggested that the anti-class II autoreactive cell-associated with syngeneic GVHD either recognizes a common class II determinant ('public ' epitope) shared by multiple strains of rats, or was polyspecific with respect to 'private' class II determinants.

AB - Lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporine (CsA) for 40 d develop a graft-vs-host disease-like syndrome (GVHD) after CsA therapy. We attempted to assess the development of auto-reactivity in these animals. Results revealed that a majority of the animals with syngeneic GVHD develop autocytotoxic T lymphocytes of the OX8 phenotype. In addition to reactivity with self, these cells were capable of lysing appropriate target cells from a variety of different rat strains. The target antigens appeared to be class II major histocompatibility antigens, because lysis could be effectively blocked by an anti-Ia monoclonal antibody. Cold target inhibition studies indicated that one effector-cell was capable of lysing various target cells, and provided evidence against a polyclonal activation of multiple anti-Ia-reactive cells. These results suggested that the anti-class II autoreactive cell-associated with syngeneic GVHD either recognizes a common class II determinant ('public ' epitope) shared by multiple strains of rats, or was polyspecific with respect to 'private' class II determinants.

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