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 Google Scholar Google Scholar Articles by Richards, H. Articles by Ager, A. Search for Related Content PubMed PubMed Citation Articles by Richards, H. Articles by Ager, A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Flu

CD62L (L-Selectin) Down-Regulation Does Not Affect Memory T Cell Distribution but Failure to Shed Compromises Anti-Viral Immunity¹

Hannah Richards^*, M. Paula Longhi^*, Kate Wright^*, Awen Gallimore^2,* and Ann Ager^2,3,*,

^* Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff and Division of Immunoregulation, Medical Research Council National Institute for Medical Research, Mill Hill, London

The down-regulation of CD62L that accompanies T lymphocyte activation is thought to redirect cells away from lymph nodes to sites of infection. In this study, CD62L was maintained on Ag-activated T cells and their distribution, and ability to clear pathogen from peripheral sites determined. CD62L was down-regulated on Ag-specific CD8 T cells in lungs of C57BL/6 mice but maintained in CD62L transgenic mice at day 8 after influenza infection. However, the numbers of influenza-specific CD8 T cells recruited were similar in CD62L transgenic and C57BL/6 mice. Memory CD8 T cell numbers in the lungs and noninvolved organs 100 days after primary infection were similar in CD62L transgenic and C57BL/6 mice, despite differing CD62L expression. Transgenic mice expressing wild-type CD62L cleared a recombinant vaccinia virus expressing an influenza-derived CD8 T cell epitope as efficiently as C57BL/6 mice. However, transgenic mice expressing a protease resistant mutant of CD62L showed significantly delayed viral clearance, despite normal CTL generation and the presence of CD107a and IFN- expressing influenza-specific CD8 T cells. These results demonstrate that CD62L down-regulation is not required for CD8 memory cells to home to sites of infection. However, their ability to clear virus is significantly compromised if CD62L shedding is abrogated.

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 the Medical Research Council United Kingdom. A.G. was supported by a Medical Research Council Senior Fellowship (G117/488).

² A.G. and A.A. contributed equally to this study.

³ Address correspondence and reprint requests to Dr. Ann Ager, Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN. E-mail address: agera{at}cardiff.ac.uk

⁴ Abbreviations used in this paper: LN, lymph node; HAU, hemagglutination units; L^tg, CD62L^ko B6 mice expressing wild-type CD62L; LP^tg, CD62L^ko B6 mice expressing shedding resistant CD62L; LdLN, lung draining LN; NP, nucleoprotein; OdLN, ovary draining LN; tet, tetramer; tg, transgene; rVV, recombinant vaccinia virus.