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

Abstract

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. © The Japanese Society for Immunology. 2006. All rights reserved.