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

Ines A. Silva, Krystyna Olkiewicz, David Askew, Jacquelyn M. Fisher, Meghana N. Chaudhary, Kevin M. Vannella, Daphne T. Deurloo, Sung W. Choi, Elizabeth M. Pierce, Shawn G. Clouthier, Chen Liu, Kenneth R. Cooke

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)598-611
Number of pages14
JournalBiology of Blood and Marrow Transplantation
Volume16
Issue number5
DOIs
StatePublished - May 1 2010

Keywords

  • Antigen presentation
  • Cytotoxicity
  • Graft-versus-leukemia
  • Immunity
  • Inflammation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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