T cell receptor clonal diversity following allogeneic marrow grafting

The advent of methods for exploring T cell clonal diversity in detail by using the reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify the CDR3 segment of the T cell receptor (TCR) Vβ gene represents a powerful tool for analyzing and monitoring T cell clones that may be responsible for graft-versus-host disease (GVHD) or specific immunity. In this report we describe studies of the posttransplant peripheral blood T cell repertoire in two patients receiving marrow grafts from unrelated donors. One patient received an unmodified T cell replete graft and the second patient received a T cell-depleted marrow graft. Both patients were matched with their donors for HLA-A and -B, but differed for a DRB1 minor mismatch. The patient receiving a TCD graft showed a progressive loss of expression of several Vβ genes during the first 6 months, although expression of some Vβ genes appeared transiently following reduction of immune suppression therapy and evidence of acute GVHD. Spectra-typing of CDR3 segments revealed evolution of new clones and clonal deletion during the post-transplant period. This method in conjunction with a functional analysis and monitoring of host-reactive clones would provide a new approach for evaluating the activity of immunosuppressive therapy.