HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krebs, P. Articles by Ludewig, B. Search for Related Content PubMed PubMed Citation Articles by Krebs, P. Articles by Ludewig, B.

Rapid Functional Exhaustion and Deletion of CTL following Immunization with Recombinant Adenovirus¹

Philippe Krebs^*,, Elke Scandella^*, Bernhard Odermatt and Burkhard Ludewig^2,*

^* Research Department, Kantonal Hospital St. Gallen, St. Gallen, Switzerland; and Institute of Experimental Immunology and Department of Pathology, University Hospital Zürich, Zürich, Switzerland

Replication-deficient adenoviruses (recombinant adenovirus (rec-AdV)) expressing different transgenes are widely used vectors for gene therapy and vaccination. In this study, we describe the tolerization of transgene-specific CTL following administration of -galactosidase (gal)-recombinant adenovirus (Ad-LacZ). Using MHC class I tetramers to track gal-specific CTL, we found that a significant expansion of gal-specific CTL was restricted to a very narrow dose range. Functional analysis revealed that adenovirus-induced gal-specific CTL produced only very low amounts of effector cytokines and were unable to exhibit cytolytic activity in a ⁵¹Cr release assay. Furthermore, Ad-LacZ vaccination failed to efficiently clear established gal-positive tumors. The impaired function of Ad-LacZ-induced CTL correlated with the presence of persisting gal Ag in the liver. A further increase in the peripheral Ag load by injection of Ad-LacZ into SM-LacZ transgenic mice which express gal as self-Ag exclusively in peripheral nonlymphoid organs, resulted in the physical deletion of gal-specific CTL. Our results indicate first that CTL deletion in the course of adenoviral vaccination is preceded by their functional impairment and second, that the outcome of rec-AdV vaccination depends critically on the Ag load in peripheral tissues.

This article has been cited by other articles:

				J. R. Lukens, M. W. Cruise, M. G. Lassen, and Y. S. Hahn Blockade of PD-1/B7-H1 Interaction Restores Effector CD8+ T Cell Responses in a Hepatitis C Virus Core Murine Model J. Immunol., April 1, 2008; 180(7): 4875 - 4884. [Abstract] [Full Text] [PDF]

				E. M. Laughlin, J. D. Miller, E. James, D. Fillos, C. C. Ibegbu, R. S. Mittler, R. Akondy, W. Kwok, R. Ahmed, and G. Nepom Antigen-Specific CD4+ T Cells Recognize Epitopes of Protective Antigen following Vaccination with an Anthrax Vaccine Infect. Immun., April 1, 2007; 75(4): 1852 - 1860. [Abstract] [Full Text] [PDF]

				T.-C. Yang, J. Millar, T. Groves, N. Grinshtein, R. Parsons, S. Takenaka, Y. Wan, and J. L. Bramson The CD8+ T Cell Population Elicited by Recombinant Adenovirus Displays a Novel Partially Exhausted Phenotype Associated with Prolonged Antigen Presentation That Nonetheless Provides Long-Term Immunity J. Immunol., January 1, 2006; 176(1): 200 - 210. [Abstract] [Full Text] [PDF]