From the Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, Boston, MA; Biotransplant, Inc, Medford, MA; and Schepens Eye Institute, Harvard Medical School, Boston, MA.
Murine mixed hematopoietic chimerism can be achieved following nonmyeloablative conditioning with cyclophosphamide, T cell–depleting monoclonal antibodies, and thymic irradiation. Donor lymphocyte infusions (DLIs) 35 days after bone marrow transplantation (BMT) convert mixed to full donor chimerism and mediate graft-versus-lymphoma effects without graft-versus-host disease. We evaluated the role of T-cell subsets in DLIs in converting mixed to full donor chimerism in a fully major histocompatibility complex–mismatched strain combination. Whereas DLIs administered on day 35 converted 100% of mixed chimeras to full donor chimerism, conversion was less frequent when either CD4 or CD8 cells were depleted, indicating that both subsets contribute to the conversion. Surprisingly, administration of CD8-depleted DLIs led to complete loss of donor chimerism in a high proportion (54%) of recipients compared with CD4-plus CD8-depleted DLIs (15%) or CD4-depleted DLIs (0%) (P < .05). DLIs administered at early time points after BMT (eg, day 21) also precipitated rejection of donor marrow by recipient 
T cells, in association with donor CD4 cell expansion and high production of interleukin 2 (IL-2), IL-4, and interferon-
. Thus, DLIs can paradoxically induce marrow rejection by residual host T cells. These results have implications for the timing of and use of subset depletion of DLIs in recipients of nonmyeloablative transplants.
Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Societe Fran?aise de Greffe de Mo?lle et Therapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and Int
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Critical role of host T cells in experimental acute graft-versus-host disease
CCR6 regulates CD4+ T-cell–mediated acute graft-versus-host disease responses
emergent autoimmunity in graft-versus-host disease
Leukocyte migration and graft-versus-host disease
New approaches for preventing and treating chronic graft-versus-host disease
Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM)
Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission