title: Host T cells affect donor T cell engraftment and graft-versus-host disease after reduced-intensity hematopoietic stem cell transplantation.
abstract: Mixed chimerism in the T cell compartment (MCT) after reduced-intensity stem cell transplantation (RIST) may influence immune repopulation with alloreactive donor T cells. We examined effects of host T cell numbers on donor T cell engraftment and recovery and on acute graft-versus-host disease (aGVHD) in a relatively homogeneous patient population with respect to residual host T cells through quantified immune depletion prior to RIST and to donor T cells by setting the allograft T cell dose of 1x10(5) CD3+ cells/kg. In this setting, 2 patterns of early donor T cell engraftment could be distinguished by day +42: (1) early and complete donor chimerism in the T cell compartment (FDCT) and (2) persistent MCT. FDCT was associated with lower residual host CD8+ T cell counts prior to transplant and aGVHD. With persistent MCT, subsequent development of aGVHD could be predicted by the direction of change in T cell donor chimerism after donor lymphocyte infusion, and no aGVHD occurred until FDCT was established. MCT did not affect recovery of donor T cell counts. These observations suggest that the relative number and alloreactivity of donor and host T cells are more important than the absolute allograft T cell dose in determining donor engraftment and aGVHD after RIST.
authors: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Nancy M
authors: NM
authors: Hardy
authors: Frances
authors: F
authors: Hakim
authors: Seth M
authors: SM
authors: Steinberg
authors: Michael
authors: M
authors: Krumlauf
authors: Romana
authors: R
authors: Cvitkovic
authors: Rebecca
authors: R
authors: Babb
authors: Jeanne
authors: J
authors: Odom
authors: Daniel H
authors: DH
authors: Fowler
authors: Ronald E
authors: RE
authors: Gress
authors: Michael R
authors: MR
authors: Bishop
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000628:therapy; D017252:CD3 Complex / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D017252:CD3 Complex
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