Early reconstitution of the T‐cell repertoire after non‐myeloablative peripheral blood stem cell transplantation is from post‐thymic T‐cell expansion and is unaffected by graft‐versus‐host disease or mixed chimaerism

Abstract

Summary. To study immune recovery after non‐myeloablative, reduced‐intensity stem cell allografts (NST) and T‐cell‐depleted myeloablative transplants (TCD), we measured T‐cell subset recovery by flow cytometry, T‐cell repertoire by spectratyping and thymic T‐cell output using a T‐cell receptor excision circle (TREC) assay. We found a rapid and comparable increase in lymphocyte numbers in both NST and TCD, supporting the presence of a powerful drive for lymphocyte recovery after transplant. Spectratyping on d 45 and 100 revealed almost complete normalization of the T‐cell repertoire in NST patients by d 45, whereas TCD patients demonstrated marked skewing of the repertoire, persisting to d 100. After NST, there was a significantly higher number of TREC‐positive CD4⁺ and CD8⁺ cells (P = 0·02 and P = 0·01 respectively). However, in both NST and TCD, early T‐cell recovery after transplant appeared to result entirely from post‐thymic T cells, the expansion pattern of which is most influenced by the starting T‐cell dose, but not markedly by graft‐versus‐host disease (GVHD) or mixed chimaerism. These results define important qualitative differences in the T‐cell repertoire according to the type of transplant schedule used.