Long-term T cell immune reconstitution in 2 SCID patients after BMT.
To evaluate the long-term reconstitution of the T cell immune repertoire in recipients of an allogeneic Bone Marrow Transplantation (allo-BMT), we have analyzed the T cell receptor (TCR) repertoire in the periphery and the T cell response against tetanus toxoid in two T- B+ Severe Combined Immunodeficiency Disease (SCID) patients more than 11 years after HLA haplo-identical allo-BMT. Our studies demonstrate that in the periphery of allo-BMT recipients, on the basis of TCR V-gene segment usage, the T cell immune repertoire long after allo-BMT is diverse, as is that of the donor. However, when donor and allo-BMT recipient were compared, differences were noted in the TCR Complementarity Determining Region 3 (CDR3) size distributions and in the T cell response against tetanus toxoid. In particular, the tetanus toxoid specific T cell clones differed in their use of HLA restriction elements, and expressed different T cell receptors. Moreover, we have uncovered donor-type tetanus toxoid specific T cell clones which were established from allo-BMT recipient derived peripheral blood lymphocytes and were found to be restricted by the non-shared recipient allele. This observation suggests a role for recipient-mediated T cell selection processes, in the thymus or at extra-thymic sites.
Godthelp
B C
BC
Department of Pediatrics, Blood Bank, Leiden University Medical Centre, The Netherlands.
van Tol
M J
MJ
Vossen
J M
JM
van den Elsen
P J
PJ
D016026:Bone Marrow Transplantation / Q000276:immunology; D002648:Child; D006801:Humans; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D016693:Receptors, Antigen, T-Cell, alpha-beta