title: Secondary lymphoid organs contribute to, but are not required for the induction of graft-versus-host responses following allogeneic bone marrow transplantation: a shifting paradigm for T cell allo-activation.
abstract: Graft-versus-host disease (GVHD) remains the major complication of allogeneic bone marrow transplantation (allo-BMT). GVHD fundamentally depends upon the activation of donor T cells by host antigen-presenting cells (APCs), but the precise location of these interactions remains uncertain. We examined the role of secondary lymphoid organs (SLO) in the induction of GVHD by using homozygous aly/aly mice that are deficient in lymph nodes (LNs) and Peyer's patches (PPs). Lethally irradiated, splenectomized, aly/aly (LN/PP/Sp-/-) mice and sham-splenectomized, aly/+ (LN/PP/Sp+/+) mice received BMT from either syngeneic (aly/aly) or allogeneic, major histocompatibility complex (MHC) disparate donors. Surprisingly, although LN/PP/Sp-/- allo-BMT recipients experience a survival advantage, they developed significant systemic and target organ GVHD that is comparable to LN/PP/Sp+/+ controls. Early after allo-BMT, the activation and proliferation of donor T cells was significantly greater in the BM cavity of LN/PP/Sp-/- mice compared to LN/PP/Sp+/+ controls. Donor T cells in LN/PP/Sp-/- mice demonstrated cytolytic activity in vitro, but Graft vs Leukemia (GVL) activity could be overcome by increasing the tumor burden. These data suggest that SLO contribute to, but are not required for, allogeneic T cell responses, and suggest that the BM may represent an alternative, albeit less efficient site for T cell activation following allo-BMT.
authors.affiliation: Department of Pediatrics, Division of Hematology and Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Ines A
authors.initials: IA
authors.lastname: Silva
authors.forename: Krystyna
authors.initials: K
authors.lastname: Olkiewicz
authors.forename: David
authors.initials: D
authors.lastname: Askew
authors.forename: Jacquelyn M
authors.initials: JM
authors.lastname: Fisher
authors.forename: Meghana N
authors.initials: MN
authors.lastname: Chaudhary
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Vannella
authors.forename: Daphne T
authors.initials: DT
authors.lastname: Deurloo
authors.forename: Sung W
authors.initials: SW
authors.lastname: Choi
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Pierce
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Clouthier
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Cooke
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D006086:Graft vs Host Disease / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous