Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC-mismatched hematopoietic cell transplantation.
Allogeneic bone marrow transplantation (BMT) is a potentially curative treatment for both inherited and acquired diseases of the hematopoietic compartment; however, its wider use is limited by the frequent and severe outcome of graft-versus-host disease (GVHD). Unfortunately, efforts to reduce GVHD by removing donor T cells have resulted in poor engraftment and elevated disease recurrence. Alternative cell populations capable of supporting allogeneic hematopoietic stem/progenitor cell engraftment without inducing GVHD could increase numbers of potential recipients while broadening the pool of acceptable donors. Although unfractionated CD4(+) T cells have not been shown to be an efficient facilitating population, CD4(+)CD25(+) regulatory cells (T-reg's) were examined for their capacity to support allogeneic hematopoietic engraftment. In a murine fully major histocompatibility complex (MHC)-mismatched BMT model, cotransplantation of donor B6 T-reg's into sublethally conditioned BALB/c recipients supported significantly greater lineage-committed and multipotential donor progenitors in recipient spleens 1 week after transplantation and significantly increased long-term multilineage donor chimerism. Donor engraftment occurred without GVHD-related weight loss or lethality and was associated with tolerance to donor and host antigens by in vitro and in vivo analyses. Donor CD4(+)CD25(+) T cells may therefore represent a potential alternative to unfractionated T cells for promotion of allogeneic engraftment in clinical hematopoietic cell transplantation.
Hanash
Alan M
AM
University of Miami Miller School of Medicine, Department of Microbiology and Immunology, PO Box 016960, Miami, FL 33101, USA.
Levy
Robert B
RB
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D006098:Granulocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006650:Histocompatibility Testing; D007108:Immune Tolerance; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
D015375:Receptors, Interleukin-2