Reconstitution of lymphocyte subpopulations after paediatric bone marrow transplantation

Abstract

Summary:We prospectively studied the reconstitution of lymphocyte subpopulations in a group of 22 children, who survived disease-free at least 6 months after allogeneic BMT for a haematological malignancy. Absolute counts of total lymphocytes, B lymphocytes, T lymphocytes, and CD4 ϩ helper T lymphocytes reached the 5th percentile (p 5 ) of age-matched reference values within 6 months after BMT in 15, 17, 7 and 2 patients, respectively. In particular, CD4 ϩ helper T lymphocyte reconstitution was very slow. Unexpectedly, CMV reactivation had a profound positive influence upon the number of CD4 ϩ helper T lymphocytes in the children. In five patients, absolute B lymphocyte counts above the 95th percentile were reached from 6 months after BMT onwards, mimicking normal ontogeny. Unlike normal ontogeny, the percentages of helper T lymphocytes expressing the 'naive' CD45RA isoform were low and those expressing the 'memory' CD45RO isoform were high in the first 3 months after BMT, as described before. Thereafter, the CD45RA:CD45RO ratio slowly normalised. Also, CD7 expression was absent on up to 90% of T lymphocytes in the first months after BMT, and on a steadily decreasing percentage thereafter, as recently described in adults. However, the absolute counts of CD45RO ϩ /CD4ϩ and CD7 Ϫ /CD4 ϩ helper T lymphocytes did not change significantly. So, we found no evidence of peripheral expansion of previously primed donor-derived 'memory' T lymphocytes during the follow-up period which spanned 1-18 months after BMT. The absolute counts of 'naive' CD45RA ϩ helper T lymphocytes did not show a faster increase after BMT than in adults, despite the presumed presence of a non-involuted thymus in children. Bone Marrow Transplantation (2000) 25, 267-275. Keywords: absolute counts; bone marrow transplantation; CD45 isoforms; CD7; children; CMV; lymphocyte subpopulations BMT is increasingly used as a potential curative therapy for haematological and other malignancies, immunodeficiency diseases, and recently also for metabolic and autoimmune Correspondence: Dr E de Vries, Leiden University Medical Centre, Dept of Paediatrics, PO Box 9600, 2300 RC Leiden, The Netherlands Received 9 October 1998; accepted 28 September 1999 disorders.1-3 Unfortunately, infectious morbidity and mortality resulting from the period of immunodeficiency early post transplant are an important side-effect of BMT.Studies on immune reconstitution after allogeneic BMT have been performed extensively in adults. [4][5][6][7][8][9] The innate immune system (phagocytes) fully recovers in the first weeks to months after BMT, but complete functional reconstitution of the adaptive immune system (B and T lymphocytes) takes much longer. Therefore, infectious complications continue to be a problem for many months after BMT. 3,10 In particular, the reconstitution of CD4 ϩ helper T lymphocytes is very slow in adults. This could be related to decreasing thymic function with age. Presumably, reconstitution of the T cell compartment shortly after BMT is mainly provided by a peri...

Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+CD3+ count reconstitution is associated with survival

“…CD4 þ CD3 þ T helper cells emerge very slowly reaching normal values 6-10 months post SCT. 3,6,30,31 Although in our study 480% of the children reached age-related 5th percentile values of the main lymphocyte subsets within the first year post SCT, the remaining children showed still very low levels of the different Tlymphocyte subsets 1 year post SCT associated with a high risk of morbidity and mortality. Similar to the CD56 þ CD3 À NK-cell reconstitution, we could show an early high peak/plateau of NK subsets expressing different KIRs.…”

T cell regeneration in pediatric allogeneic stem cell transplantation

“…26,29 The recovery of the naive CD4 þ T lymphocytes post HSCT has been shown to be protracted also in children. 30,31 In previous studies, data on immune reconstitution has been compared with either healthy, age-matched controls 31 or within subgroups. We used age-matched, immunosuppressed, non-transplanted controls to monitor the effects of previous chemotherapy and conditioning.…”

In vivo T-cell dynamics during immune reconstitution after hematopoietic stem cell gene therapy in adenosine deaminase severe combined immune deficiency

“…Our data show that the recovery of the peripheral T-cell compartment after HSC GT for ADA-SCID is driven by both naive and memory cells, to an extent comparable to what is observed in our age-matched cohort of patients undergoing allogeneic BMT and in previous reports in pediatric and adult BMT recipients. [13][14][15] Our cohort of pediatric BMT patients was heterogeneous and included only a minority of patients with ADA-SCID. Nevertheless, we did not find statistically significant differences within this cohort by comparing the absolute number of lymphocytes or T-cell subsets counts with respect to conditioning or diagnosis (data not shown; Fig E2).…”

“…12 After BMT, the reconstitution of the peripheral T cells is mainly driven by memory cells, particularly at early follow-up, in both pediatric and adult recipients. [13][14][15] There is limited information on the relative contribution of the different T-cell subsets and the various mechanisms of differentiation during the T-cell pool reconstitution after GT treatment.…”