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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3673-3681. Prepublished online as a Blood First Edition Paper on August 9, 2007; DOI 10.1182/blood-2007-04-087171. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-087171v1 110/10/3673    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Scumpia, P. O. Articles by Moldawer, L. L. Search for Related Content PubMed PubMed Citation Articles by Scumpia, P. O. Articles by Moldawer, L. L. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis Philip O. Scumpia1, Matthew J. Delano1, Kindra M. Kelly-Scumpia2, Jason S. Weinstein2, James L. Wynn1, Robert D. Winfield1, Changqing Xia3, Chun Shiang Chung4, Alfred Ayala4, Mark A. Atkinson3, Westley H. Reeves2, Michael J. Clare-Salzler3, and Lyle L. Moldawer1 Departments of 1 Surgery, 2 Medicine, and 3 Pathology, University of Florida College of Medicine, Gainesville; and 4 Division of Surgical Research/Department of Surgery, Rhode Island Hospital and Brown University School of Medicine, Providence Apoptosis of CD4+ T cells and TH2 polarization are hallmarks of sepsis-induced immunoparalysis. In this study, we characterized sepsis-induced adaptive immune dysfunction and examined whether improving T-cell effector function can improve outcome to sepsis. We found that septic mice produced less antigen-specific T-cell–dependent IgM and IgG2a antibodies than sham-treated mice. As early as 24 hours after sepsis, CD4+ T cells proliferated poorly to T-cell receptor stimulation, despite normal responses to phorbol myristate acetate and ionomycin, and possessed decreased levels of CD3. Five days following immunization, CD4+ T cells from septic mice displayed decreased antigen-specific proliferation and production of IL-2 and IFN- but showed no difference in IL-4, IL-5, or IL-10 production. Treatment of mice with anti-GITR agonistic antibody restored CD4+ T-cell proliferation, increased TH1 and TH2 cytokine production, partially prevented CD3 down-regulation, decreased bacteremia, and increased sepsis survival. Depletion of CD4+ T cells but not CD25+ regulatory T cells eliminated the survival benefit of anti-GITR treatment. These results indicate that CD4+ T-cell dysfunction is a key component of sepsis and that improving T-cell effector function may be protective against sepsis-associated immunoparalysis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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