Infusion of select leukemia-reactive TCR Vβ+ T cells provides graft-versus leukemia responses with minimization of graft-versus-host disease following murine hematopoietic stem cell transplantation

T-cell receptor (TCR) V beta -expression analysis by complementarity-determining region 3 (CDR3)-size spectratyping can identify the reactive populations in an immunologic response. This analysis was used in this study to characterize the V beta responses of C57BL/6 (B6) CD4(+) and CD8(+) T cells directed to either alloantigen (against [B6xDBA/2]F1; anti-H2(d)) or the syngeneic myeloid leukemia A/IMB3.19. V beta families exhibiting reactivity to the leukemia cells were then enriched for and administered in both syngeneic and allogeneic hematopoietic stem cell transplantation (HSCT) models to assess in vivo graft-versus-leukemia (GVL) potential. In syngeneic transplants, enrichment for pools of selected V beta families (V beta7, -11, and -13) of T cells or for a single V beta family (V beta7) of CD4(+) T cells conveyed a beneficial GVL response to the recipients. Furthermore, in the haploidentical allogeneic model, both V beta6,7-enriched donor B6 T cells and V beta7-enriched CD4(+) T cells exhibited significant GVL responses with concomitant minimization of graft-versus-host disease (GVHD) development compared with equal numbers of unfractionated T cells. These results suggest that CDR3-size spectratype analysis of and subsequent selection from donor T-cell repertoires can be an effective approach to separate GVL and GVHD potential following allogeneic HSCT.