Inflammatory chemokine receptors regulate CD8+T cell contraction and memory generation following infection

Kohlmeier, J. E. et al. (2011) Inflammatory chemokine receptors regulate CD8+T cell contraction and memory generation following infection. Journal of Experimental Medicine, 208(8), pp. 1621-1634. (doi: 10.1084/jem.20102110) (PMID:21788409) (PMCID:PMC3149221)

134476.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial Share Alike.



The development of T cell memory from naive precursors is influenced by molecular cues received during T cell activation and differentiation. In this study, we describe a novel role for the chemokine receptors CCR5 and CXCR3 in regulating effector CD8+ T cell contraction and memory generation after influenza virus infection. We find that Ccr5−/− Cxcr3−/− cells show markedly decreased contraction after viral clearance, leading to the establishment of massive numbers of memory CD8+ T cells. Ccr5−/− Cxcr3−/− cells show reduced expression of CD69 in the lung during the peak of infection, which coincides with differential localization and the rapid appearance of memory precursor cells. Analysis of single chemokine receptor–deficient cells revealed that CXCR3 is primarily responsible for this phenotype, although there is also a role for CCR5 in the enhancement of T cell memory. The phenotype could be reversed by adding exogenous antigen, resulting in the activation and contraction of Ccr5−/− Cxcr3−/− cells. Similar results were observed during chronic Mycobacterium tuberculosis infection. Together, the data support a model of memory CD8+ T cell generation in which the chemokine-directed localization of T cells within infected tissues regulates antigen encounter and controls the extent of CD8+ T cell activation and differentiation, which ultimately regulates effector versus memory cell fate decisions.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Perona-Wright, Dr Georgia
Authors: Kohlmeier, J. E., Reiley, W. W., Perona-Wright, G., Freeman, M. L., Yager, E. J., Connor, L. M., Brincks, E. L., Cookenham, T., Roberts, A. D., Burkum, C. E., Sell, S., Winslow, G. M., Blackman, M. A., Mohrs, M., and Woodland, D. L.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Experimental Medicine
Publisher:Rockefeller University Press
ISSN (Online):1540-9538
Published Online:25 July 2011
Copyright Holders:Copyright © 2011 Kohlmeier et al.
First Published:First published in Journal of Experimental Medicine 208(8):1621-1634
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record