Rizzitelli Alexandra, Hawkins Edwin, Todd Hilary, Hodgkin Philip D, Shortman Ken
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Int Immunol. 2006 Mar;18(3):415-23. doi: 10.1093/intimm/dxh382. Epub 2006 Jan 13.
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.
稳态小鼠的CD8(+)脾树突状细胞（DCs）在体外培养中刺激CD4 T细胞增殖的能力不如CD8(-) DC亚群。然而，基于CD69和CD25表达的上调，我们发现这两种DC亚型在激活CD4 T细胞方面同样有效。此外，我们发现在进入第一次分裂之前，T细胞死亡速率没有差异。然后，我们追踪了羧基荧光素二乙酸琥珀酰亚胺酯标记的T细胞，并采用定量模型详细评估了CD4 T细胞在受到CD8(+)或CD8(-) DC刺激后的扩增过程。在两种DC培养物中，大多数T细胞在第一次分裂前复制其DNA所需的时间相似。然而，与CD8(-) DC培养相比，CD8(+) DC中CD4 T细胞群体在随后分裂中的进展有所减少。这与每个分裂阶段存活T细胞损失的增加有关。因此，激活后与分裂相关的T细胞死亡是CD4 T细胞对CD8(+) DC反应降低的主要因素。
