Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response
Abstract Superantigens (sAgs) are bacterial virulence factors that induce a state of immune hyperactivation by forming a bridge between certain subsets of T cell receptor (TCR) β chains on T lymphocytes, and class II major histocompatibility complex (MHC-II) molecules; this cross-linking leads to in...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54074-8 |
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| author | Heran Zhang Ian R. Monk Jessica Braverman Claerwen M. Jones Andrew G. Brooks Timothy P. Stinear Linda M. Wakim |
| author_facet | Heran Zhang Ian R. Monk Jessica Braverman Claerwen M. Jones Andrew G. Brooks Timothy P. Stinear Linda M. Wakim |
| author_sort | Heran Zhang |
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| description | Abstract Superantigens (sAgs) are bacterial virulence factors that induce a state of immune hyperactivation by forming a bridge between certain subsets of T cell receptor (TCR) β chains on T lymphocytes, and class II major histocompatibility complex (MHC-II) molecules; this cross-linking leads to indiscriminate T cell activation, cytokine storm and toxic shock. Here we show that sAg exposure drives the preferential expansion of naive and central memory T cell subsets, but not effector or resident memory T cells, which instead, hyper release pro-inflammatory cytokines. A targeted therapeutic approach to minimise cytokine release by effector memory T cells attenuated sAg-induced cytokine release. Irrespective of antigen experience, sAg activation does not render mature T cells permanently dysfunctional, and full restoration of effector function is observed following a transient and reversible anergy. Moreover, we show that in the face of sAg induced immune hyperactivation, an intact bacterium-specific CD4+ T cell response can be mounted. |
| format | Article |
| id | doaj-art-c05a1fab140c4c649629a5df6a0761ef |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c05a1fab140c4c649629a5df6a0761ef2024-11-17T12:37:41ZengNature PortfolioNature Communications2041-17232024-11-0115111710.1038/s41467-024-54074-8Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune responseHeran Zhang0Ian R. Monk1Jessica Braverman2Claerwen M. Jones3Andrew G. Brooks4Timothy P. Stinear5Linda M. Wakim6Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and ImmunityDepartment of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and ImmunityDepartment of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and ImmunityBiomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash UniversityDepartment of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and ImmunityDepartment of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and ImmunityDepartment of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and ImmunityAbstract Superantigens (sAgs) are bacterial virulence factors that induce a state of immune hyperactivation by forming a bridge between certain subsets of T cell receptor (TCR) β chains on T lymphocytes, and class II major histocompatibility complex (MHC-II) molecules; this cross-linking leads to indiscriminate T cell activation, cytokine storm and toxic shock. Here we show that sAg exposure drives the preferential expansion of naive and central memory T cell subsets, but not effector or resident memory T cells, which instead, hyper release pro-inflammatory cytokines. A targeted therapeutic approach to minimise cytokine release by effector memory T cells attenuated sAg-induced cytokine release. Irrespective of antigen experience, sAg activation does not render mature T cells permanently dysfunctional, and full restoration of effector function is observed following a transient and reversible anergy. Moreover, we show that in the face of sAg induced immune hyperactivation, an intact bacterium-specific CD4+ T cell response can be mounted.https://doi.org/10.1038/s41467-024-54074-8 |
| spellingShingle | Heran Zhang Ian R. Monk Jessica Braverman Claerwen M. Jones Andrew G. Brooks Timothy P. Stinear Linda M. Wakim Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response Nature Communications |
| title | Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response |
| title_full | Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response |
| title_fullStr | Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response |
| title_full_unstemmed | Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response |
| title_short | Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response |
| title_sort | staphylococcal superantigens evoke temporary and reversible t cell anergy but fail to block the development of a bacterium specific cellular immune response |
| url | https://doi.org/10.1038/s41467-024-54074-8 |
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