International Immunology Advance Access published online on January 13, 2006
International Immunology, doi:10.1093/intimm/dxh382
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1 The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
* To whom correspondence should be addressed. 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.
Received September 23, 2005
Accepted December 9, 2005
Article
The proliferative response of CD4 T cells to steady-state CD8+ dendritic cells is restricted by post-activation death
Alexandra Rizzitelli 1,
Edwin Hawkins 1,
Hilary Todd 1,
Philip D. Hodgkin 1,
and
Ken Shortman 1 *
Ken Shortman, E-mail: shortman{at}wehi.edu.au
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