CD28 Blockade Induces Division-Dependent Down-Regulation of Interleukin-2 Receptor Alpha

• Type of Material: Article
• Authors: Mandy L Ford, Emory University; Linda L. Stempora, Emory University; Christian P Larsen, Emory University
• Language: English
• Date: 2011-01-15
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Elsevier B.V. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.trim.2010.11.002
• Title of Journal or Parent Work: Transplant Immunology
• ISSN: 0966-3274
• Volume: 24
• Issue: 2
• Start Page: 94
• End Page: 99
• Keywords: T cell activation; costimulation blockade; interleukin-2; precursor frequency
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Background Blockade of T cell costimulatory molecules represents a promising new method of attenuating donor-reactive T cell responses to promote graft survival following transplantation. However, recent studies in murine models have shown the presence of an initial high frequency of naïve donor-reactive T cells may render this strategy ineffective. Methods In this report, we examined the phenotypic changes associated with CD28 blockade on T cells stimulated at increasing precursor frequencies in vitro. Results We found that treatment with the CD28 blocker CTLA-4 Ig resulted in downregulation of the alpha chain of the IL-2 receptor (CD25) in a division-dependent manner. Significantly, blockade of the CD28 pathway was more effective in down-regulating CD25 when the donor-reactive T cell population was present at low as compared to high precursor frequency. Conclusions These results imply that treatment with CD28 blockers and anti-CD25 mAbs may cooperate in promoting graft survival under conditions of low MHC matching where the donor-reactive T cell precursor frequency is high.