title: 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 beta-chain immunophenotyping or spectratyping. Using beta-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 beta 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.
authors.affiliation: Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington, USA. jstorek@ucalgary.ca
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yiping
authors.initials: Y
authors.lastname: Liu
authors.forename: Richard
authors.initials: R
authors.lastname: Nash
authors.forename: Peter
authors.initials: P
authors.lastname: McSweeney
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
mesh_terms: D000328:Adult; D018952:Antigens, CD34; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology / Q000628:therapy*; D019653:Myeloablative Agonists / Q000008:administration & dosage; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood* / Q000276:immunology; D012595:Scleroderma, Systemic / Q000097:blood / Q000276:immunology / Q000628:therapy*; D013997:Time Factors; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
chemical_list: D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003520:Cyclophosphamide