To investigate the mechanisms of human T-cell reconstitution following allogeneic haematopoietic stem cell transplantation (alloSCT), I analysed the clonal composition of human cytomegalovirus (HCMV)-specific and EBV-specific CD8+ T cells in 9 alloSCT recipients and their donors. All virus-specific CD8+ T-cell clones isolated from post-alloSCT recipients contained DNA of donor origin. Following transplantation from HCMV-seropositive donors into HCMV-seropositive recipients, immunodominant donor HCMV-specific clones underwent early expansion and were maintained long-term. In contrast, donor HCMV-specific clones were undetectable in two HCMV-seronegative EBV-seropositive recipients whereas transferred EBV-specific clones were maintained in the same recipients, suggesting that transferred clones require antigen for their maintenance. Following transplantation from seronegative donors into seropositive recipients, the delayed primary response of virus-specific CD8+ T-cells containing donor DNA suggested that new antigen-specific T-cells in the recipient arose from donor-derived progenitor cells. Two HCMV-seropositive recipients developed a different clonal composition from their HCMV-seropositive donors, with delayed persistent expansion of HCMV-specific clones that were undetectable in the donor or in the recipient during the first 5 months after transplantation; these may represent expansion of novel clones generated from donor-derived progenitor cells. I conclude that after alloSCT there is late diversification of the virus-specific CD8+ T-cell clonal repertoire in response to persistent viral antigen.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:599296 |
| Date | January 2003 |
| Creators | Gandhi, M. K. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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