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Evidence for superantigen production by Yersinia pseudotuberculosis
1Department of Allergy and Immunology, National Children's Medical Research Center, Tokyo, Japan.
Abstract:
Yersinia pseudotuberculosis is an enteric pathogen that induces a variety of clinical symptoms, fever, scarlatiniform rash, diarrhea, vomiting, and arthritis. Characteristic histopathologic findings in Y. pseudotuberculosis infection such as lymphoid hyperplasia, typically seen in mesenteric lymph nodes, suggest that the stimulation of a large proportion of T lymphocytes may be involved in the pathogenesis of this infection. In this study, we assessed the mitogenic activity of culture supernatants of the clinical isolates of Y. pseudotuberculosis and investigated the mechanism by which these culture sups activate T cells. The culture sups, as well as partially purified fractions obtained by gel filtration, were found to selectively stimulate T cells bearing V beta 3, V beta 9, V beta 13.1, and V beta 13.2 compared with stimulation by anti-CD3. Furthermore, fibroblasts transfected with different HLA class II molecules, either HLA-DPw9, -DQw6, -DR1, or -DR4 Dw15, were capable of presenting Y. pseudotuberculosis culture supernatants to purified T cells. The T cell response to this sup was not restricted by donor HLA-DR types and was not neutralized by antibodies against the known staphylococcal superantigens, Staphylococcal enterotoxin (SE)A, SEB, SEC2, SED, SEE, and TSST1. These results suggest that Y. pseudotuberculosis produces superantigenic toxins that may mediate some of the systemic illnesses associated with infection by this organism.
Insights
Yersinia pseudotuberculosis produces superantigenic toxins that activate specific T cells. These toxins may contribute to the systemic symptoms observed in Y. pseudotuberculosis infections.
Area of Science:
- Immunology
- Microbiology
- Pathogenesis
Background:
- Yersinia pseudotuberculosis causes various symptoms including fever, rash, diarrhea, and arthritis.
- Histopathology shows lymphoid hyperplasia, suggesting T lymphocyte involvement in infection pathogenesis.
Purpose of the Study:
- To assess the mitogenic activity of Y. pseudotuberculosis culture supernatants.
- To investigate the mechanism of T cell activation by these supernatants.
Main Methods:
- Assessed mitogenic activity of Y. pseudotuberculosis culture supernatants and purified fractions.
- Investigated T cell stimulation using specific T cell receptor V beta chains and HLA class II-transfected fibroblasts.
- Tested neutralization with antibodies against known staphylococcal superantigens.
Main Results:
- Culture supernatants selectively stimulated T cells bearing V beta 3, V beta 9, V beta 13.1, and V beta 13.2.
- Fibroblasts presented Y. pseudotuberculosis supernatants to T cells via HLA class II molecules (HLA-DPw9, -DQw6, -DR1, -DR4 Dw15).
- T cell response was not HLA-DR restricted and not neutralized by anti-staphylococcal superantigen antibodies.
Conclusions:
- Yersinia pseudotuberculosis produces superantigenic toxins.
- These toxins may mediate systemic illnesses associated with Y. pseudotuberculosis infection.