Exoenzyme S from Pseudomonas aeruginosa induces apoptosis in T lymphocytes

Exoenzyme S from Pseudomonas aeruginosa is a unique T cell mitogen; it is a powerful immunostimulus that activates a large proportion of T cells, but results in delayed and reduced lymphocyte proliferation. This study was per formed to explain the discrepancy between early T cell activation and subse quent proliferation. Studies revealed that exoenzyme S induced rapid and un sustained surface expression of CD69, hut could not induce interleukin-2 re ceptor alpha (IL-2R alpha) up-regulation on T cells. IL-2 was undetectable in supernatants and addition of rIL-2 could not reverse the unresponsivenes s, indicating that anergy was not involved. Exoenzyme S induced membrane ph osphatidylserine translocation, DNA hypodiploidy, and DNA fragmentation, im plicating apoptosis as the mechanism for the unresponsiveness. Exoenzyme S- iuduced apoptosis shows features of both propriocidal and death by neglect, suggesting shared characteristics of an intermediate pathway. Thus, a Pseu domonas exoproduct induces T cell apoptosis, which may contribute to the pa thogenesis of Pseudomonas infections in diseases such as cystic fibrosis.