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 performed to explain the discrepancy between early T cell activation and subsequent proliferation. Studies revealed that exoenzyme S induced rapid and unsustained surface expression of CD69, but could not induce interleukin-2 receptor alpha (IL-2R alpha) up-regulation on T cells. IL-2 was undetectable in supernatants and addition of rIL-2 could not reverse the unresponsiveness, indicating that anergy was not involved. Exoenzyme S induced membrane phosphatidylserine translocation, DNA hypodiploidy, and DNA fragmentation, implicating apoptosis as the mechanism for the unresponsiveness. Exoenzyme S-induced apoptosis shows features of both propriocidal and death by neglect, suggesting shared characteristics of an intermediate pathway. Thus, a Pseudomonas exoproduct induces T cell apoptosis, which may contribute to the pathogenesis of Pseudomonas infections in diseases such as cystic fibrosis.
Bruno
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TF
Department of Microbiology and Infectious Diseases, University of Calgary, Alberta, Canada.
Woods
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DE
Mody
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D036002:ADP Ribose Transferases / Q000276:immunology / Q000494:pharmacology*; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation; D008934:Mitogens / Q000276:immunology / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011990:Receptors, Transferrin; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D001427:Bacterial Toxins; C068126:CD71 antigen; D007376:Interleukin-2; D008934:Mitogens; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D036002:ADP Ribose Transferases; C444820:exoenzyme S