title: Trauma patients' elevated tumor necrosis related apoptosis inducing ligand (TRAIL) contributes to increased T cell apoptosis.
abstract: Immunosuppression resulting from excessive post-trauma apoptosis of hyperactivated T cells is controversial. TRAIL mediated T cell apoptosis decreases highly activated T cells' responses. Caspase-10, a particular TRAIL target, was increased in trauma patients' T cells with concomitantly elevated plasma TRAIL levels. These patients' T cells developed anergy, implicating increased TRAIL-mediated T cell apoptosis in post-trauma T cell anergy. Control T cells cultured with patients' sera containing high TRAIL levels increased their caspase-10 activity and apoptosis. Stimulated primary T cells are TRAIL apoptosis resistant. Increased plasma thrombospondin-1 and T cell expression of CD47, a thrombospondin-1 receptor, preceded patients' T cell anergy. CD47 triggering of T cells increased their sensitivity to TRAIL-induced apoptosis. Augmentation of T cell TRAIL-induced apoptosis was secondary to CD47 triggered activation of the Src homology-containing phosphatase-1 (SHP-1) and was partially blocked by a SHP-1 inhibitor. We suggest that combined post-trauma CD47 triggering, SHP-1 mediated NFκB suppression, and elevated TRAIL levels increase patients' CD47 expressing T cell apoptosis, thus contributing to subsequent T cell anergy.
authors.affiliation: Immunobiology & Stress Response Laboratory, Department of Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Bandyopadhyay
authors.forename: Paul E
authors.initials: PE
authors.lastname: Bankey
authors.forename: Carol L
authors.initials: CL
authors.lastname: Miller-Graziano
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D051928:CD47 Antigen / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D053455:Caspase 10 / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D044967:Serum / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology / Q000494:pharmacology*; D019700:Thrombospondin 1 / Q000235:genetics / Q000276:immunology; D014947:Wounds and Injuries / Q000276:immunology* / Q000473:pathology
chemical_list: D051928:CD47 Antigen; C497894:CD47 protein, human; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D019700:Thrombospondin 1; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D053455:Caspase 10; C506438:CASP10 protein, human