Ex Vivo-Expanded Hematopoietic Cell Graft Recipients Exhibit T Cell Repertoire Diversity Similar to That Seen After Conventional Stem Cell Transplants

Abstract

The feasibility of using ex vivo-expanded hematopoietic progenitor cells to reconstitute hematopoiesis after high-dose chemotherapy is presently being examined. Early studies have shown that myeloid and erythroid hematopoiesis can be successfully reconstituted after high-dose chemotherapy and ex vivo-expanded hematopoietic cell transplantation. The lymphoid reconstitution, however, has not been addressed previously. In this study, we examined the diversity of the T cell receptor V beta chain (TCRBV) repertoires in 5 breast cancer patients who were transplanted with ex vivo-expanded bone marrow mononuclear cells as the only source of hematopoietic graft. Using the TCRBV third complementarity determining region (CDR3) fingerprinting methodology, it is shown that CD4(+) and CD8(+) T cell subsets after ex vivo-expanded hematopoietic cell graft transplants exhibit TCRBV diversities that are similar in complexity when compared to those seen after conventional autologous peripheral blood stem cell transplants (PBSCT). No apparent difference in the extent of CDR3 diversity was found between ex vivo expanded and conventional autologous PBSCT recipients when the CD4(+) and CD8(+) subsets were further separated into CD45RA(+) "naïve" and CD45RO(+) "memory" subsets. The diversity of the CD45RA(+) naïve subsets was as complex as that of the CD45RO(+) memory subsets. These results indicate that T cell repertoire diversification is not further compromised when ex vivo-expanded hematopoietic cells are used instead of autologous peripheral blood stem cells as the only source of graft.