T-cell activation, proliferation and apoptosis in primary Listeria monocytogenes infection

Listeria monocytogenes infection of mice leads to a rapid expansion of activated T cells, followed by a decline in specific cells once the bacteria are eliminated. In order to define the relationship between T-cell proliferation and activation, and to investigate the role of apoptosis in limiting the expansion, the expression of activation markers, uptake of 5-bromo-2'-deoxyuridine (BrdU) in vivo and the incidence of apoptosis was investigated. Increased numbers of T cells expressing the activated phenotype CD25(+) , CD44(hi) and CD62L(lo) were detected 4 days after infection. Expression of CD25 (IL-2Ralpha chain) on CD4(+) and CD8(+) T cells peaked at this time and returned to normal by day 7. In contrast, CD44(hi) and CD62L(lo) persisted, with the maximum proportion occurring at 7 days after infection. This was accompanied by a burst of in vivo proliferation of CD4(+) and CD8(+) T cells occurring between day 5 and 7. Apoptosis, which is presumably needed to control this expansion of T cells, also peaked at 7 days after infection. Apoptosis occurred preferentially amongst T cells which had proliferated. Most but not all proliferating T cells had down-regulated their CD62L marker. While most apoptotic T cells were CD62L(lo) , again not all had down-regulated this marker. Hence, CD25 expression peaked early, but expression of other activation markers, in vivo proliferation and apoptosis coincided after Listeria infection. T cells that had proliferated were over-represented in the apoptotic population.