The Journal of Experimental Medicine
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Published online 20 March 2006 doi:10.1084/jem.20050711
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 4, 897-906
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ARTICLE

 CD4 memory T cells survive and proliferate but fail to differentiate in the absence of CD40

Megan MacLeod1, Mark J. Kwakkenbos1, Alison Crawford1, Sheila Brown1, Brigitta Stockinger2, Koen Schepers3, Ton Schumacher3, and David Gray1

1 Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh EH9 3JT, UK
2 Division of Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
3 Department of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands

CORRESPONDENCE David Gray: d.gray{at}ed.ac.uk

Secondary T cell responses are enhanced because of an expansion in numbers of antigen-specific (memory) cells. Using major histocompatibility complex class II tetramers we have tracked peptide-specific endogenous (non–T cell receptor transgenic) CD4 memory T cells in normal and in costimulation-deficient mice. CD4 memory T cells were detectable after immunization for more than 200 days, although decay was apparent. Memory cells generated in CD40 knockout mice by immunization with peptide-pulsed wild-type dendritic cells survived in the absence of CD40 and proliferated when boosted with peptide (plus adjuvant) in a CD40-independent fashion. However, differentiation of the memory cells into cytokine-producing effector cells did not occur in the absence of CD40. The data indicate that memory cells can be generated without passing through the effector cell stage.


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