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
Feb 1, 1994·European Journal of Immunology·S MiyawakiY Shibata
Jul 1, 1996·International Immunology·R ShinkuraT Honjo
Jun 16, 1997·The Journal of Experimental Medicine·U KarrerR M Zinkernagel
Nov 20, 1998·The Journal of Clinical Investigation·K R CookeJ L Ferrara
Aug 3, 1999·The Journal of Clinical Investigation·T TeshimaJ L Ferrara
Jun 20, 2001·The Journal of Clinical Investigation·K R CookeJ L Ferrara
Aug 4, 2001·Immunity·J W HomeisterJ B Lowe
Sep 6, 2001·The Journal of Experimental Medicine·G SmithsonJ B Lowe
Oct 31, 2001·Transplantation·T R ZieglerB R Blazar
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
Feb 26, 2005·Clinical and Experimental Immunology·K TeramotoT Hibi
Mar 15, 2005·Clinical and Experimental Immunology·K MatsuzakiS Miura
Apr 28, 2005·Blood·Andreas BeilhackRobert S Negrin
Sep 15, 2005·Blood·Lisbeth A WelniakWilliam J Murphy
Oct 18, 2005·Nature Medicine·Pavan ReddyJames L M Ferrara
Nov 9, 2007·Blood·Andreas BeilhackRobert S Negrin
Feb 21, 2008·Blood·Britt E AndersonMark J Shlomchik
Mar 4, 2008·Nature Immunology·Anita SapoznikovSteffen Jung
Citations
Oct 13, 2011·Cancer Immunology, Immunotherapy : CII·Elisabeth ErsværOystein Bruserud
Oct 23, 2014·Stem Cells·Jeffery J AulettaKenneth R Cooke
Feb 6, 2014·Stem Cells·Hong LiNing Mao
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
Jun 27, 2017·Bone Marrow Transplantation·M Y ShapiraA I Bloom
Apr 22, 2011·Laboratory Animals·Hideaki InagakiYukihisa Matsuda
Jul 13, 2019·Blood Advances·Sarah Morin-ZormanWarren D Shlomchik
Nov 4, 2017·Annual Review of Pathology·Eric Perkey, Ivan Maillard