Role of antigen-presenting cells in activation of human T cells by the streptococcal M protein superantigen: requirement for secreted and membrane-associated costimulatory factors
| Autor: | H. Ohnishi, M A Tomai, Malak Kotb, M. E. Dockter, Bo Wang, Gipsy Majumdar, A. M. Geller |
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| Jazyk: | angličtina |
| Rok vydání: | 1993 |
| Předmět: |
T-Lymphocytes
Immunology Antigen presentation education Bacterial Toxins Antigen-Presenting Cells Biology Lymphocyte Activation Microbiology Enterotoxins Immune system Cell–cell interaction Antigen Bacterial Proteins Superantigen Humans Antigen-presenting cell Cells Cultured Antigens Bacterial Superantigens Histocompatibility Antigens Class II T lymphocyte Molecular biology Infectious Diseases cardiovascular system Parasitology Calcium Carrier Proteins Intracellular circulatory and respiratory physiology Research Article Bacterial Outer Membrane Proteins |
| Popis: | The requirements for T-cell activation by the streptococcal superantigen (SAg), pepsin-extracted M protein from type 5 streptococci (pep M5), were studied by monitoring Ca2+ influx and cell proliferation. Cells from a pep M5-specific T-cell line showed no change in intracellular Ca2+ levels in response to pep M5 when added alone or with freshly isolated autologous antigen-presenting cells (APC). However, after being incubated with pep M5 overnight, the APC secreted soluble factors that together with pep M5 induced a marked increase in intracellular Ca2+ levels in pep M5-specific T cells or freshly isolated, purified T cells. Removal of the SAg from the overnight APC-derived supernatants resulted in loss of the Ca(2+)-mobilizing activity, which was restored within seconds of addition of SAg, suggesting that both the SAg and the soluble factors synergize to induce the Ca2+ influx. Induction of cell proliferation required additional signals inasmuch as the activated APC-derived supernatant failed to synergize with pep M5 to induce the proliferation of purified T cells and required the presence of phorbol myristate acetate for this activity. Metabolically inactive, fixed APC were impaired in their ability to present pep M5 to T cells. Presentation of pep M5 by fixed APC was, however, restored when the APC-derived soluble costimulatory factors were added to the culture. Our data suggest that pep M5-induced activation of T cells is dependent on APC-derived soluble factors and an APC membrane-associated costimulatory molecule(s). These interactions may be important in regulating the in vivo responses to M proteins, could contribute to the severity or progression of infections with Streptococcus pyogenes, and may influence the susceptibility of individuals to its associated nonsuppurative autoimmune sequelae. |
| Databáze: | OpenAIRE |
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