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

• Published in: Blood Vol. 98; no. 3; pp. 868 - 876
• Main Authors: Miura, Yuji, Thoburn, Christopher J., Bright, Emilie C., Sommer, Matthias, Lefell, Susan, Ueda, Mikio, Nakao, Shinji, Hess, Allan D.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-08-2001; The Americain Society of Hematology
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Base Sequence; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Breast Neoplasms - complications; Breast Neoplasms - therapy; CD8-Positive T-Lymphocytes - immunology; Clone Cells - immunology; Clone Cells - pathology; Complementarity Determining Regions - chemistry; Cyclosporine - administration & dosage; Cyclosporine - pharmacology; Cytotoxicity Tests, Immunologic; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - immunology; Graft vs Host Disease - pathology; Hematopoietic Stem Cell Transplantation; HLA Antigens - genetics; HLA-DR Antigens - blood; HLA-DRB1 Chains; Humans; Immunoglobulin Joining Region - genetics; Immunoglobulin Variable Region - genetics; Lymphoma, Non-Hodgkin - complications; Lymphoma, Non-Hodgkin - therapy; Male; Medical sciences; Middle Aged; Phenotype; Receptors, Antigen, T-Cell - drug effects; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Autologous; Autoimmunity; Human; Immunopathology; Immune response; Stem cell; HLA-DR-System; Major histocompatibility system; Class II histocompatibility antigen; Hematopoietic cell; Graft versus host reaction; Autograft; Immunological investigation; T-Lymphocyte; Graft; Complication; Ciclosporin; Immunologic repertoire; Immunosuppressive agent
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.3.868

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.