title: Common lymphoid progenitors rapidly engraft and protect against lethal murine cytomegalovirus infection after hematopoietic stem cell transplantation.
abstract: Lymphoid deficiency after allogeneic hematopoietic cell transplantation (HCT) results in increased susceptibility to infection; however, transplantation of mature lymphocytes frequently results in a serious complication known as graft-versus-host disease (GVHD). Here we demonstrate in mice that both congenic as well as allogeneic transplantation of low numbers of highly purified common lymphoid progenitors (CLPs)-a rare population of lymphoid-lineage-committed bone marrow cells-accelerates immune reconstitution after lethal irradiation and rescue with hematopoietic stem cells (HSCs). After congenic transplantation, 3 x 10(3) CLPs protected against murine cytomegalovirus (MCMV) infection at a level roughly equivalent to 107 unfractionated lymph node cells. In the allogeneic model of matched unrelated donor HSC transplantation, cotransplantation of 3 x 10(3) CLPs protected thymus-bearing as well as thymectomized hosts from MCMV infection and attenuated disease severity. Immunohistochemistry in combination with antibody depletion of T and natural killer (NK) cells confirmed that CLP-derived as well as residual host lymphocytes contribute to antiviral protection. Importantly, transplantation of allogeneic CLPs provided a durable antiviral immunity without inducing GVHD. These data support the potential for composing grafts with committed progenitors to reduce susceptibility to viral infection following HCT.
authors.affiliation: Department of Medicine, Division of Bone Marrow Transplantation, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Arber
authors.forename: Andrew
authors.initials: A
authors.lastname: BitMansour
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Sparer
authors.forename: John P
authors.initials: JP
authors.lastname: Higgins
authors.forename: Edward S
authors.initials: ES
authors.lastname: Mocarski
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Janice M Y
authors.initials: JM
authors.lastname: Brown
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D002469:Cell Separation; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000517:prevention & control*; D004198:Disease Susceptibility; D006086:Graft vs Host Disease / Q000517:prevention & control; D006183:H-2 Antigens / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D016867:Immunocompromised Host; D007694:Killer Cells, Natural / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013934:Thymectomy; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D006183:H-2 Antigens