title: A repertoire-independent and cell-intrinsic defect in murine GVHD induction by effector memory T cells.
abstract: Effector memory T cells (T(EM)) do not cause graft-versus-host disease (GVHD), though why this is has not been elucidated. To compare the fates of alloreactive naive (T(N)) or memory (T(M)) T cells, we developed a model of GVHD in which donor T cells express a transgene-encoded TCR specific for an antigenic peptide that is ubiquitously expressed in the recipient. Small numbers of naive TCR transgenic (Tg) T cells induced a robust syndrome of GVHD in transplanted recipients. We then used an established method to convert TCR Tg cells to T(M) and tested these for GVHD induction. This allowed us to control for the potentially different frequencies of alloreactive T cells among T(N) and T(M), and to track fates of alloreactive T cells after transplantation. T(EM) caused minimal, transient GVHD whereas central memory T cells (T(CM)) caused potent GVHD. Surprisingly, T(EM) were not inert: they, engrafted, homed to target tissues, and proliferated extensively, but they produced less IFN-γ and their expansion in target tissues was limited at later time points, and local proliferation was reduced. Thus, cell-intrinsic properties independent of repertoire explain the impairment of T(EM), which can initiate but cannot sustain expansion and tissue damage.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520-8035, USA.
authors.forename: Kathryn W
authors.initials: KW
authors.lastname: Juchem
authors.forename: Britt E
authors.initials: BE
authors.lastname: Anderson
authors.forename: Cuiling
authors.initials: C
authors.lastname: Zhang
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: McNiff
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: Donna L
authors.initials: DL
authors.lastname: Farber
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
authors.forename: Warren D
authors.initials: WD
authors.lastname: Shlomchik
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010641:Phenotype; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse