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 Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dudani, R. Articles by Sad, S. Search for Related Content PubMed PubMed Citation Articles by Dudani, R. Articles by Sad, S.

Mutation in the Fas Pathway Impairs CD8⁺ T Cell Memory¹

National Research Council of Canada, Institute for Biological Sciences, Ottawa, Ontario, Canada

Fas death pathway is important for lymphocyte homeostasis, but the role of Fas pathway in T cell memory development is not clear. We show that whereas the expansion and contraction of CD8⁺ T cell response against Listeria monocytogenes were similar for wild-type (WT) and Fas ligand (FasL) mutant mice, the majority of memory CD8⁺ T cells in FasL mutant mice displayed an effector memory phenotype in the long-term in comparison with the mainly central memory phenotype displayed by memory CD8⁺ T cells in WT mice. Memory CD8⁺ T cells in FasL mutant mice expressed reduced levels of IFN- and displayed poor homeostatic and Ag-induced proliferation. Impairment in CD8⁺ T cell memory in FasL mutant hosts was not due to defective programming or the expression of mutant FasL on CD8⁺ T cells, but was caused by perturbed cytokine environment in FasL mutant mice. Although adoptively transferred WT memory CD8⁺ T cells mediated protection against L. monocytogenes in either the WT or FasL mutant hosts, FasL mutant memory CD8⁺ T cells failed to mediate protection even in WT hosts. Thus, in individuals with mutation in Fas pathway, impairment in the function of the memory CD8⁺ T cells may increase their susceptibility to recurrent/latent infections.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Canadian Institutes of Health Research.

² Address correspondence and reprint requests to Dr. Subash Sad, Institute for Biological Sciences, National Research Council of Canada, 1200 Montreal Road, Building M-54, Ottawa, Ontario, Canada K1A 0R6. E-mail address: subash.sad{at}nrc.ca

³ Abbreviations used in this paper: FasL, Fas ligand; LCMV, lymphocytic choriomeningitis virus; LM, Listeria monocytogenes; SLE, systemic lupus erythematosus.