title: Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning.
abstract: Graft rejection remains a major obstacle in allogeneic hematopoietic SCT following reduced-intensity conditioning (RIC-SCT), particularly after cord blood transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft rejection was associated with activation and expansion of donor-reactive host T cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells are at least partly involved in host T-cell activation. We then evaluated if such an expansion of host T cells could be associated with graft rejection after RIC-CBT. Expansion of residual host lymphocytes was observed in 4/7 patients with graft rejection at 3 weeks after CBT, but in none of the 17 patients who achieved engraftment. These results suggest the crucial role of residual host T cells after RIC-SCT in graft rejection and expansion of host T cells could be a marker of graft rejection. Development of more efficient T cell-suppressive conditioning regimens may be necessary in the context of RIC-SCT.
authors.affiliation: 1] Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan [2] Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Koyama
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medical Science, Sapporo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Hashimoto
authors.affiliation: Department of Hematology, Kurume University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nagafuji
authors.affiliation: Department of Hematology, Hamanomachi General Hospital, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Eto
authors.affiliation: Internal medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Aoyama
authors.affiliation: Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Iwasaki
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: G R
authors.initials: GR
authors.lastname: Hill
authors.affiliation: 1] Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan [2] Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Akashi
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medical Science, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Teshima
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D046528:Chimerism; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D023421:Models, Animal; D012189:Retrospective Studies; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult