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.

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Ines A SilvaKenneth R Cooke

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 ...Continue Reading

References

Dec 15, 1991·Journal of Immunological Methods·P Matzinger
Aug 12, 2003·Nature Medicine·Markus FeuererVolker Schirrmacher
Sep 25, 2003·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Diana Whitaker-MenezesGeorge F Murphy
Dec 9, 2003·Trends in Molecular Medicine·Volker SchirrmacherPhilipp Beckhove
Mar 9, 2004·Experimental Hematology·Lisbeth A WelniakWilliam J Murphy
Sep 17, 2004·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Hideyasu NagamatsuSoichiro Miura

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Citations

Oct 20, 2012·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Nadir AskenasyJerry Stein
Oct 8, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Kenneth R CookeBruce R Blazar
Apr 22, 2011·Laboratory Animals·Hideaki InagakiYukihisa Matsuda
Nov 4, 2017·Annual Review of Pathology·Eric Perkey, Ivan Maillard

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