THE ROLE OF ????- AND ????-T CELLS IN ALLOGENEIC DONOR MARROW ON ENGRAFTMENT, CHIMERISM, AND GRAFT-VERSUS-HOST DISEASE1:

Background. We previously characterized a facilitating cell (FC) in mouse marrow that enables engraftment of allogeneic hematopoietic stem cells (HSCs) without causing graft-versus-host disease (GVHD). The FC shares some cell surface molecules with T cells (Thy1(+), CD3epsilon(+), CD8(+), CD5(+), and CD2(+)) but is T-cell receptor (TCR) negative. Historically, depletion of CD3(+) or CD8(+) cells from rat marrow was associated with an increased rate of failure of engraftment. In this study, we evaluated whether depletion of alphabeta- and gammadelta-TCR+ T cells from donor marrow would retain engraftment potential yet avoid GVHD. Methods. Wistar-Furth rats were conditioned with 950 cGy of total body irradiation and transplanted with ACI bone marrow processed to remove either alphabeta-TCR+, gammadelta-TCR+, or alphabeta- plus gammabeta-TCR+ T cells. Recipients were typed for chimerism at 28 days and monthly thereafter. Results. Recipients of marrow depleted of alphabeta- (group A), gammadelta- (group B), or alphabeta- and gammadelta-TCR+ T cells (group C) engrafted and had an average chimerism level of 73.0 +/- 8.3%, 92.3 +/- 9.2%, and 46.3 +/- 32.8%, respectively. Aggressive T-cell depletion did not remove the FC population (CD8(+)/CD3(+)/TCR-). Group A and group B both developed GVHD, with a higher incidence of GVHD in group B compared to group A. None of the recipients in group C developed GVHD. Conclusions. These data demonstrate that depletion of T cells from rat marrow does not impair engraftment of HSCs, indirectly supporting the existence of FCs in rat marrow. Moreover, donor alphabeta- and gammadelta-TCR+ T cells contribute to GVHD in a nonredundant fashion, although alphabeta-TCR+ T cells are more potent as the effector cells. Finally, the level of donor chimerism is influenced by the composition of the graft, because recipients of marrow that contain alphabeta-TCR+ T cells exhibited significantly higher donor chimerism compared to recipients of marrow depleted of both alphabeta- and gammadelta-TCR+ T cells.