• Gautam Bandyopadhyay, Paul E Bankey, and Carol L Miller-Graziano.
• Immunobiology & Stress Response Laboratory, Department of Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
• Clin. Immunol. 2012 Oct 1; 145 (1): 44-54.

AbstractImmunosuppression 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.Copyright © 2012 Elsevier Inc. All rights reserved.

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