LONG-TERM T-CELL IMMUNE RECONSTITUTION IN 2 SCID PATIENTS AFTER BMT

To evaluate the long-term reconstitution of the T cell immune repertoi re in recipients of an allogeneic Bone Marrow Transplantation (allo-BM T), we have analyzed the T cell receptor (TCR) repertoire in the perip hery and the T cell response against tetanus toroid in two T-B+ Severe Combined Immunodeficiency Disease (SCID) patients more than 11 years after HLA haploidentical 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 Determini ng Region 3 (CDR3) size distributions and in the T cell response again st tetanus toroid. In particular, the tetanus toroid specific T cell c lones differed in their use of HLA restriction elements, and expressed different T cell receptors. Moreover, we have uncovered donor-type te tanus toroid specific T cell clones which were established from allo-B MT recipient derived peripheral blood lymphocytes and were found to be restricted by the nonshared recipient allele. This observation sugges ts a role for recipient-mediated T cell selection processes, in the th ymus or at extra-thymic sites. (C) American Society for Histocompatibi lity and Immunogenetics, 1998. Published by Elsevier Science Inc.