Early Recovery of CD4 T Cell Receptor Diversity after “Lymphoablative” Conditioning and Autologous CD34 Cell Transplantation

Abstract 

T cell diversity posttransplantation is thought to be severely restricted, based on T cell receptor β-chain immunophenotyping or spectratyping. Using β-chain sequencing, we studied CD4 T cell diversity in 2 adult patients undergoing “lymphoablative” conditioning with cyclophosphamide (Cy), total body irradiation (TBI), and antithymocyte globulin (ATG) and autologous transplantation of hematopoietic cells depleted of T cells by enrichment for CD34 cells. The indication for the transplantation was systemic sclerosis (SSc) or multiple sclerosis (MS). Pretransplantation, the estimated number of distinct β chains (the minimum number of CD4 T cell clones) in the 2 patients was 600,000 to 700,000, similar to the number in a healthy control. This number was 200,000 to 500,000 at 1 month posttransplantation and 400,000 to 1,600,000 at 12 months posttransplantation. In conclusion, the number of T cells early after lymphoablative conditioning and autologous CD34 cell transplantation may be more diverse than previously appreciated, possibly because many T cell clones survive the conditioning or are reinfused with the graft. Thus, the therapy may not be completely T cell lymphoablative.

Key Words: T lymphocytes, Autologous hematopoietic cell transplantation, Multiple sclerosis, Systemic sclerosis