title: Alloantigen affinity and CD4 help determine severity of graft-versus-host disease mediated by CD8 donor T cells.
abstract: TCR affinity dictates T cell selection in the thymus and also has a high impact on the fate of peripheral T cells. Graft-vs-host disease (GVHD) is a pathological process initiated by activation of donor T cells after adoptive transfer into an allogeneic recipient. How TCR affinity affects the potential of alloreactive T cells to induce GVHD is unclear. Using alloreactive CD4+ and CD8+ TCR transgenic (Tg) T cells, GVHD models are presented that allow for the visualization of how CD8+ alloreactive T cells behave in response to alloantigens with different TCR affinity in the absence or presence of CD4 help. In a nonmyeloablative transplant model where GVHD lethality is due to marrow aplasia, alloreactive CD8+ TCR Tg T cells induced significantly more severe GVHD in the recipients that express an intermediate-affinity alloantigen than in the recipients that express a high-affinity alloantigen. In a myeloablative transplant model where GVHD lethality is due to epithelium injury, CD8+ TCR Tg cells were also more pathogenic in the recipients with an intermediate-affinity alloantigen than in those with a high-affinity alloantigen. The presence of alloreactive CD4+ TCR Tg cells enhanced the potential of CD8+ TCR Tg cells to cause GVHD in recipients with an intermediate-, but not with a high-, affinity alloantigen. These findings underscore that alloantigen affinity and CD4 help control the fate and pathogenicity of alloreactive CD8+ T cells in vivo.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. yuxz@moffitt.usf.edu
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Yu
authors.forename: Michael H
authors.initials: MH
authors.lastname: Albert
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000818:Animals; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017690:Cell Transplantation; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology*; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D022423:Myeloid Cells / Q000166:cytology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D007519:Isoantigens; D011947:Receptors, Antigen, B-Cell