Induction of apoptosis in lymphoid tissues of mice after intramuscular injection of enterotoxigenic Escherichia coli enterotoxin.

Although it has been reported that intravenous injection of Escherichia coli enterotoxin induces atrophies of the thymus and spleen by necrosis, the toxin injected intramuscularly to mice induced atrophies of both tissues, which were associated with apoptosis of lymphocytes. Apoptosis predominantly occurred in the thymus and increased in a time-dependent manner up to 26 h and faint ladder band patterns of DNA were observed at 36 h. Although the high dose of toxin also induced in vitro apoptosis in cultured thymocytes, the toxin was not detected in the serum at levels sufficient to cause in vitro apoptosis after intramuscular administration. By flow cytometric analysis, CD4+ CD8+ double-positive T cell and CD45+ positive B cell numbers were found to be mainly decreased in thymus and spleen, respectively, of mice. These results suggest that the atrophies of thymus and spleen by intramuscular administration of the toxin to mice are due to apoptosis of CD4+ CD8+ double-positive T and CD45+ positive B cells, respectively, but the toxin does not reach these cells via the circulation. A different mechanism from that in vitro in cultured cells might be involved in the induction of apoptosis in vivo.