Characterization of the T-cell repertoire in autologous graft-versus-host disease (GVHD): Evidence for the involvement of antigen-driven T-cell response in the development of autologous GVHD

Yuji Miura, Christopher J. Thoburn, Emilie C. Bright, Matthias Sommer, Susan Lefell, Mikio Ueda, Shinji Nakao, Allan D. Hess

Research output: Contribution to journalArticle

Abstract

Administration of cyclosporine A (CsA) after autologous stem cell transplantation elicits an autoimmune syndrome with pathology similar to graft-versus-host disease (GVHD). This syndrome, termed autologous GVHD, is associated with the appearance of autoreactive T cells directed at major histocompatibility class (MHC) class II antigens. In the rat model of autologous GVHD, clonal analysis reveals that the effector T cells are highly conserved and recognize a peptide from the invariant chain peptide presented by MHC class II. Although human autologous GVHD effector T cells share a similar phenotypic specificity, clonality of the response in humans has not been determined. To examine the human effector T-cell response, the T-cell repertoire of peripheral blood lymphocytes was assessed by complementarity-determining region 3 (CDR3) size distribution analysis and T-cell clonotype analysis in 26 patients treated with CsA after transplantation. Autologous GVHD developed in 3 of 4 patients with human leukocyte antigen (HLA)-DRB1*0701, and clonal expansions of β-chain variable region (BV)16+ T cells were shared. Clonal expansions within BV15+ and BV22+ T cells were also detected in 4 of 6 patients with HLA-DRB1*1501 and in 3 of 4 patients with HLA-DRB1*0401, respectively. Sequencing of BV16 cDNA for which the CDR3 size pattern exhibited apparent clone predominance revealed an identical CDR3 peptide sequence in 2 different patients, one with HLA-DRB1*0701 and the other with HLA-DRB1*1502. These findings indicate that the discrete antigen-driven expansion of T cells is involved in autologous GVHD.

Original languageEnglish (US)
Pages (from-to)868-876
Number of pages9
JournalBlood
Volume98
Issue number3
DOIs
StatePublished - Aug 1 2001

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T-cells
Graft vs Host Disease
Grafts
T-Lymphocytes
Antigens
HLA Antigens
Complementarity Determining Regions
Histocompatibility
Peptides
Cyclosporine
Transplantation (surgical)
Lymphocytes
Histocompatibility Antigens Class II
Stem Cell Transplantation
Pathology
Stem cells
Rats
Blood
Complementary DNA
Clone Cells

ASJC Scopus subject areas

  • Hematology

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Characterization of the T-cell repertoire in autologous graft-versus-host disease (GVHD) : Evidence for the involvement of antigen-driven T-cell response in the development of autologous GVHD. / Miura, Yuji; Thoburn, Christopher J.; Bright, Emilie C.; Sommer, Matthias; Lefell, Susan; Ueda, Mikio; Nakao, Shinji; Hess, Allan D.

In: Blood, Vol. 98, No. 3, 01.08.2001, p. 868-876.

Research output: Contribution to journalArticle

Miura, Yuji ; Thoburn, Christopher J. ; Bright, Emilie C. ; Sommer, Matthias ; Lefell, Susan ; Ueda, Mikio ; Nakao, Shinji ; Hess, Allan D. / Characterization of the T-cell repertoire in autologous graft-versus-host disease (GVHD) : Evidence for the involvement of antigen-driven T-cell response in the development of autologous GVHD. In: Blood. 2001 ; Vol. 98, No. 3. pp. 868-876.
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abstract = "Administration of cyclosporine A (CsA) after autologous stem cell transplantation elicits an autoimmune syndrome with pathology similar to graft-versus-host disease (GVHD). This syndrome, termed autologous GVHD, is associated with the appearance of autoreactive T cells directed at major histocompatibility class (MHC) class II antigens. In the rat model of autologous GVHD, clonal analysis reveals that the effector T cells are highly conserved and recognize a peptide from the invariant chain peptide presented by MHC class II. Although human autologous GVHD effector T cells share a similar phenotypic specificity, clonality of the response in humans has not been determined. To examine the human effector T-cell response, the T-cell repertoire of peripheral blood lymphocytes was assessed by complementarity-determining region 3 (CDR3) size distribution analysis and T-cell clonotype analysis in 26 patients treated with CsA after transplantation. Autologous GVHD developed in 3 of 4 patients with human leukocyte antigen (HLA)-DRB1*0701, and clonal expansions of β-chain variable region (BV)16+ T cells were shared. Clonal expansions within BV15+ and BV22+ T cells were also detected in 4 of 6 patients with HLA-DRB1*1501 and in 3 of 4 patients with HLA-DRB1*0401, respectively. Sequencing of BV16 cDNA for which the CDR3 size pattern exhibited apparent clone predominance revealed an identical CDR3 peptide sequence in 2 different patients, one with HLA-DRB1*0701 and the other with HLA-DRB1*1502. These findings indicate that the discrete antigen-driven expansion of T cells is involved in autologous GVHD.",
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