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 human s 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 fr eshly isolated T cells from healthy volunteers and patients with severe pne umonia were identified as apoptotic. However, during culture the rate of ap optosis in peripheral blood T cells from patients was 3.0 +/- 0.9%; and inc reased further in the presence of anti-CD3 (7.4 +/- 2.1%) and decreased whe n IL-2 was added (4.4 +/- 1.3%). In contrast, no changes were observed in h ealthy volunteers on addition of anti-CD3. Further, anti-CD3 significantly increased the susceptibility to apoptosis of CD45RO+ T cells, but not CD45R A+ T cells from patients, and the percentage of CD45RO+ T cells in patients was significantly higher than that in healthy volunteers. Flowcytometric a nalysis revealed the expression level of Fas to be higher in the patients t han healthy volunteers. Collectively, these findings demonstrated that bact eria-reactive T cells were more susceptible to AICD and that Fas-FasL pathw ays of apoptosis were involved. AICD of CD45RO+ T cells, therefore, provide s an explanation for the loss of bacteria-reactive T cells during bacterial infection.