Factors affecting thymic function after allogeneic hematopoietic stem celltransplantation

Hematopoietic stem cell transplantation (HSCT) is followed by profound immu nodeficiency. Thymic function is necessary for de novo generation of T cell s after HSCT. Circulating CD45RA(+) naive T-cell levels are predictive of a ntigen-specific T-cell responses in the absence of graft-versus-host diseas e (GVHD). These T cells may not represent recent thymic emigrants, since na ive T cells may maintain this phenotype if not antigen-activated. To accura tely measure thymic output after HSCT and determine the factors that influe nce thymic function, T-cell receptor excision circles (TRECs) were examined in CD4(+) and CD8(+) cells from a cross-section of patients following HSCT . TREC levels rose weeks after HSCT and could be detected in patients 6 yea rs after HSCT. TREC levels correlated with the frequency of phenotypically naive T cells, indicating that such cells were not expanded progeny of naiv e T cells present in the donor graft. Chronic GVHD was the most important f actor that predicted low TREC levels even years after HSCT. Patients with a history of resolved GVHD had decreased numbers of TREC, compared with thos e with no GVHD. Because few adults had no history of GVHD, it was not possi ble to determine whether age alone inversely correlated with TREC levels. R ecipients of cord blood grafts had no evidence of decreased TREC induced by immunosuppressive prophylaxis drugs. Compared with unrelated donor grafts, recipients of matched sibling grafts had higher TREC levels. Collectively, these data suggest that thymopoiesis is inhibited by GVHD. Larger studies will be needed to determine the independent contributions of age and prepar ative regimen to posttransplant thymopoietic capacity. (Blood. 2001;91:1458 -1466) (C) 2001 by The American Society of Hematology.