Developmentally arrested pro-T cells (CD4-8-, IL-2R+, HSA++) of RAG-1-deficient mice appear to express low levels of CD3 molecules in the absence of T cell receptor (TcR) chains at their surface, while developmentally arrested pre-T cells of TcR alpha-deficient mice express low levels of a disulfide-linked TcR beta chain in association with CD3 molecules. Cross-linking of the CD3 modules on pro-T cells of RAG-1-/- mice in vivo, with either of two different CD3 epsilon-specific monoclonal antibodies, induces differentiation of these pro-T cells into pre-T cells (CD4+8+, IL-2R-, HSA+), concomitant with a rapid expansion of the thymic T cell compartment, up to 175-fold within 12 days. The same effects can be produced by introduction of a mutant TcR beta transgene lacking most of the variable domain (delta V-TcR beta) into the RAG-1-/- background. These experiments suggest that cross-linking of the CD3 modules on pro-T cells mimics the signaling function expected of the pre-TcR complex, which is found at the surface of pre-T cells prior to functional TcR alpha gene rearrangement. The variable domain of the TcR beta chain is apparently not essential for inducing these aspects of T cell development.

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...