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 ¼ 0AE02 and P ¼ 0AE01 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.

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

“…[41][42][43] Although previous investigations suggested poor T cell reconstitution due to thymic injury by GvHD, 44 recently published data showed no differences in T cell subset counts and TREC levels in dependence of GvHD. 45 This is in line with our observations, where we found no significant differences in T cell reconstitution with respect to incidence and extent of GvHD. B lymphocyte recovery returned to normal 1 year after HSCT and was delayed in case of steroids as a part of GvHD prophylaxis, but not influenced by the occurrence of GvHD or following immunosuppression with the use of steroids after HSCT.…”

Peripheral T-cell expansion and low infection rate after reduced-intensity conditioning and allogeneic blood stem cell transplantation

“…It is possible that the reduction of median TREC levels observed between M þ 7.5 and M þ 11 could be due to the low number of patients, but we can also hypothesize that this reduction may result either from activation-induced cell death of naı¨ve cells or, more probably, from dilution of the TRECpositive cells, through peripheral naı¨ve T-cell division. 31 This result is in line with data from Bahceci et al, 32 who observed a progressive decrease of TREC contents from day 14 to day 180 after RIC-PBSCT and concluded that early reconstitution resulted from post-thymic T-cell expansion. Our data further suggest that recent thymic emigrants may enter a peripheral expansion that would be added to the initial peripheral expansion of infused T cells.…”

Immune reconstitution after allogeneic stem cell transplantation with reduced-intensity conditioning regimens

“…41 It has been suggested that the more rapid recovery of T cells after RIC-SCT could be the result of peripheral expansion of infused T cells instead of an actual preservation of thymic function. Bahceci et al 32 observed that naïve CD4 þ T-cell numbers were significantly higher in RIC-SCT patients at all time points other than 1 year after transplant in comparison with T-cell depleted MAC-SCT. The levels of TRECs were also significantly higher in RIC recipients than in MAC patients at 45 days after transplant; however, they gradually decreased after the SCT.…”

“…25,31,32 Taken together, these qualitative differences might lead to faster development of effective immune response against infectious agents and residual host malignant cells.…”