High Frequency Alloreactive T Cells Augment Effector Function of Low Frequency CD8+ T Cell Responses Under CD28/CD154 Blockade

• Type of Material: Article
• Authors: Tamara L. Floyd, Emory University; Steven B. Orr, Emory University; Shana M. Coley, Emory University; Samantha S. Hanna, Emory University; Maylene E. Wagener, Emory University; Allan D Kirk, Emory University; Christian P Larsen, Emory University; Mandy L Ford, Emory University
• Language: English
• Date: 2010-05-27
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Lippincott Williams & Wilkins, Inc.
• Final Published Version (URL): http://ovidsp.tx.ovid.com/sp-3.11.0a/ovidweb.cgi?QS2=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
• Title of Journal or Parent Work: Transplantation
• ISSN: 0041-1337
• Volume: 89
• Issue: 10
• Start Page: 1208
• End Page: 1217
• Grant/Funding Information: National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID; This work was supported by NIH K22 AI079409 to MLF and NIH R37 AI40519 to CPL.
• Keywords: precursor frequency; T-lymphocyte; tolerance; costimulation; transplantation
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Background Blockade of costimulatory molecules is a potent method of inducing long-term graft survival. We have previously addressed the issue of donor-reactive T cell precursor frequency on relative costimulation dependence, and found that the presence of a high precursor frequency of donor-reactive CD8+ T cells resulted in costimulation blockade-resistant graft rejection, whereas the presence of a low-frequency donor-reactive population did not. To address the mechanisms by which high frequency T cells obviated the requirement for costimulation, we asked whether a low frequency population responding concomitantly with a high frequency response also demonstrated costimulation independence. Methods A model system was established in which B6 mice containing a low frequency of anti-mOVA responders and a high frequency of anti-BALB/c responders received a skin graft from B6.mOVAxBALB/c F1 donors in the presence or absence of CTLA-4 Ig/anti-CD154 costimulatory blockade. Results Results revealed that in the presence of costimulation blockade, high frequency anti-BALB/c T cells augmented the effector activity of low frequency anti-mOVA T cells, but did not enhance the accumulation of anti-mOVA T cells capable of mediating graft rejection. Conclusions These results demonstrate that both antigen-specific and antigen-independent factors contribute to the relative costimulation-independence of high frequency T cell responses.