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