Early recovery of CD4 T cell receptor diversity after "lymphoablative" conditioning and autologous CD34 cell transplantation.
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.
Storek
Jan
J
Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington, USA. jstorek@ucalgary.ca
Zhao
Zhao
Z
Liu
Yiping
Y
Nash
Richard
R
McSweeney
Peter
P
Maloney
David G
DG
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
D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003520:Cyclophosphamide