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International Immunology Advance Access originally published online on January 13, 2006
International Immunology 2006 18(3):415-423; doi:10.1093/intimm/dxh382
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

The proliferative response of CD4 T cells to steady-state CD8+ dendritic cells is restricted by post-activation death

Alexandra Rizzitelli, Edwin Hawkins, Hilary Todd, Philip D. Hodgkin and Ken Shortman

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia

Correspondence to: K. Shortman; E-mail: shortman{at}wehi.edu.au

CD8+ splenic dendritic cells (DCs) from steady-state mice are less effective than the CD8 DC subset in their capacity to stimulate CD4 T cell proliferation in culture. However, we found that the two DC subtypes were equally potent at activating CD4 T cells, based on up-regulation of CD69 and CD25 expression. Also, we found no difference in the rate of T cell death prior to entry into the first division. We then tracked carboxyfluorescein diacetate succinimidyl ester-labeled T cells and employed a quantitative model to assess in detail the CD4 T cell expansion process in response to stimulation with CD8+ or with CD8 DCs. The time required for most T cells to replicate their DNA prior to the first division was similar in both DC cultures. However, progression of the CD4 T cell population through subsequent divisions was reduced in CD8+ DCs compared with CD8 DC culture. This was associated with an increased loss of viable T cells at each division. Post-activation, division-associated T cell death is therefore a major factor in the reduced response of CD4 T cells to CD8+ DCs.

Keywords: dendritic cells, modelling, T cells, T cell proliferation

Transmitting editor: A. Kelso


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