Involvement of apoptosis in activation-induced cell death of bacteria-reactive human CD45RO+ T cells

Although the identity of the T cells that protect against bacteria in humans remains unknown, it is clear that patients with bacterial infection have reduced numbers of T cells in their blood. Here we have determined whether this T cell loss is a consequence of bacterial antigen-mediated activation-induced cell death (AICD). By flowcytometric analysis, less than 0.3% of freshly isolated T cells from healthy volunteers and patients with severe pneumonia were identified as apoptotic. However, during culture the rate of apoptosis in peripheral blood T cells from patients was 3.0 +/- 0.9%; and increased further in the presence of anti-CD3 (7.4 +/- 2.1%) and decreased when IL-2 was added (4.4 +/- 1.3%). In contrast, no changes were observed in healthy volunteers on addition of anti-CD3. Further, anti-CD3 significantly increased the susceptibility to apoptosis of CD45RO+ T cells, but not CD45RA+ T cells from patients, and the percentage of CD45RO+ T cells in patients was significantly higher than that in healthy volunteers. Flowcytometric analysis revealed the expression level of Fas to be higher in the patients than healthy volunteers. Collectively, these findings demonstrated that bacteria-reactive T cells were more susceptible to AICD and that Fas-FasL pathways of apoptosis were involved. AICD of CD45RO+ T cells, therefore, provides an explanation for the loss of bacteria-reactive T cells during bacterial infection.