title: Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells.
abstract: Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation. Effector memory T cells (T(EM)) do not cause GVHD but engraft and mount immune responses, including graft-versus-tumor effects. One potential explanation for the inability of T(EM) to cause GVHD is that T(EM) lack CD62L and CCR7, which are instrumental in directing naive T cells (T(N)) to lymph nodes (LN) and Peyer patches (PP), putative sites of GVHD initiation. Thus T(EM) should be relatively excluded from LN and PP, possibly explaining their inability to cause GVHD. We tested this hypothesis using T cells deficient in CD62L or CCR7, transplant recipients lacking PNAd ligands for CD62L, and recipients without LN and PP or LN, PP, and spleen. Surprisingly, CD62L and CCR7 were not required for T(N)-mediated GVHD. Moreover, in multiple strain pairings, GVHD developed in recipients that lacked LN and PP. Mild GVHD could even be induced in mice lacking all major secondary lymphoid tissues (SLT). Conversely, enforced constitutive expression of CD62L on T(EM) did not endow them with the ability to cause GVHD. Taken together, these data argue against the hypothesis that T(EM) fail to induce GVHD because of inefficient trafficking to LN and PP.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Britt E
authors.initials: BE
authors.lastname: Anderson
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Taylor
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: McNiff
authors.forename: Dhanpat
authors.initials: D
authors.lastname: Jain
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: Angela
authors.initials: A
authors.lastname: Panoskaltsis-Mortari
authors.forename: Ann
authors.initials: A
authors.lastname: Ager
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Warren D
authors.initials: WD
authors.lastname: Shlomchik
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D006086:Graft vs Host Disease / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation; D016130:Immunophenotyping; D019041:L-Selectin / Q000502:physiology*; D051379:Mice; D054400:Receptors, CCR7 / Q000502:physiology*; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019041:L-Selectin