title: Endogenous memory CD8 T cells are activated within cardiac allografts without mediating rejection.
abstract: Endogenous memory CD8 T cells infiltrate MHC-mismatched cardiac allografts within 12-24 h posttransplant in mice and are activated to proliferate and produce IFN-γ. To more accurately assess the graft injury directly imposed by these endogenous memory CD8 T cells, we took advantage of the ability of anti-LFA-1 mAb given to allograft recipients on days 3 and 4 posttransplant to inhibit the generation of primary effector T cells. When compared to grafts from IgG-treated recipients on day 7 posttransplant, allografts from anti-LFA-1 mAb-treated recipients had increased numbers of CD8 T cells but these grafts had marked decreases in expression levels of mRNA encoding effector mediators associated with graft injury and decreases in donor-reactive CD8 T cells producing IFN-γ. Despite this decreased activity within the allograft, CD8 T cells in allografts from recipients treated with anti-LFA-1 mAb continued to proliferate up to day 7 posttransplant and did not upregulate expression of the exhaustion marker LAG-3 but did have decreased expression of ICOS. These results indicate that endogenous memory CD8 T cells infiltrate and proliferate in cardiac allografts in mice but do not express sufficient levels of functions to mediate overt graft injury and acute rejection.
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH; Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH; Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Setoguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Hattori
authors.forename: S
authors.initials: S
authors.lastname: Iida
authors.forename: W M
authors.initials: WM
authors.lastname: Baldwin
authors.forename: R L
authors.initials: RL
authors.lastname: Fairchild
mesh_terms: D064591:Allografts; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation; D060889:Inducible T-Cell Co-Stimulator Protein / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D014181:Transplantation Immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D060889:Inducible T-Cell Co-Stimulator Protein; D023201:CD40 Ligand; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse
keywords: Cardiac allograft; T cell activation/inactivation; T cell graft infiltration; memory
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