Modulation of T-dependent recall humoral immunity by Staphylococcal enterotoxin B (63.12)
| Autor: | William Lee, David Janik |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:63.12-63.12 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Some microbial toxins are superantigens (SAg) that target large numbers of CD4 T cells. We previously showed that the SAg SEB can lead to memory CD4 T cell inactivation (anergy). Given that SAgs target TCRs independently of their peptide-binding properties, memory T cell help for unrelated antigens might be impaired. Here we show that SEB prevented T-dependent recall humoral immunity. In a mouse model, ovalbumin (OVA)-specific, Vβ8-expressing memory CD4 T cells provided help to hapten-specific B cells after challenge with the T-dependent antigen, TNP-OVA. Only when specific memory T cells were present did the mice make TNP-specific secondary (IgG) humoral responses; otherwise a primary (IgM) humoral response was observed. Exposure of the immune mice to SEB prior to challenge with TNP-OVA led to a loss of IgG production, indicating impaired memory helper function. Aberrant recall immunity was long-lived, as even 3 weeks after exposure to SEB, immunization with TNP-OVA resulted in IgM, but not IgG, anti-TNP Ab. Comparable numbers of carrier-specific T cells were present in SEB-treated and control mice, suggesting that anergic memory cells were maintained in vivo. Memory cell anergy occurred due to Fyn kinase-dependent negative signaling, and Fyn-deficient memory cells promoted IgG production even after SEB exposure. Hence, bacterial toxins can target memory helper cells to eliminate recall responses to unrelated antigens, suggesting a potential need for re-vaccination. |
| Databáze: | OpenAIRE |
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