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

Administration of cyclosporine A (CsA) after autologous stem cell transplan tation elicits an autoimmune syndrome with pathology similar to graft-versu s-host disease (GVHD). This syndrome, termed autologous GVHD, Is associated with the appearance of autoreactive T cells directed at major histocompati bility class (MHC) class 11 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 fl. Although human autologous GVHD effector T cells share a similar phenot ypic specificity, clonality of the response In humans has not been determin ed. To examine the human effector T-cell response, the T-cell repertoire of peripheral blood lymphocytes was assessed by complementarity-determining r egion 3 (CDR3) size distribution analysis and T-cell clonotype analysis in 26 patients treated with CsA after transplantation. Autologous GVHD develop ed in 3 of 4 patients with human leukocyte antigen (HLA)-DRB1*0701, and clo nal expansions of beta -chain variable region (BV)16(+) T cells were shared . Clonal expansions within BV15(+) and BV22(+) T cells were also detected i n 4 of 6 patients with HLA-DRB1*1501 and in 3 of 4 patients with HLA-DRB1*0 401, respectively. Sequencing of BV16 cDNA for which the CDR3 size pattern exhibited apparent clone predominance revealed an identical CDR3 peptide se quence in 2 different patients, one with HLA-DRB1*0701 and the other with H LA-DRB1*1502. These findings Indicate that the discrete antigen-driven expa nsion of T cells is involved In autologous GVHD. (C) 2001 by The American S ociety of Hematology.