Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response

• Published in: Nature communications 2024-11, Vol.15 (1), p.9872-17, Article 9872
• Main Authors: Zhang, Heran, Monk, Ian R., Braverman, Jessica, Jones, Claerwen M., Brooks, Andrew G., Stinear, Timothy P., Wakim, Linda M.
• Format: Article
• Language: English
• Subjects: 13; 13/31; 631/250/1619/554/1898; 631/250/2152/1566/1618; 631/250/2152/1566/2493; 631/250/2499; 631/326/41/2534; 64; 64/60; Anergy; Animals; Antigen-presenting cells; Antigens; Bacteria; Bridge failure; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; Cell activation; Clonal Anergy - immunology; Crosslinking; Cytokine storm; Cytokines; Cytokines - immunology; Cytokines - metabolism; Effector cells; Female; Humanities and Social Sciences; Immune response; Immune response (cell-mediated); Immune system; Immunity, Cellular; Immunological memory; Inflammation; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Memory cells; Memory T Cells - immunology; Mice; Mice, Inbred C57BL; multidisciplinary; Science; Science (multidisciplinary); Septic shock; Staphylococcal Infections - immunology; Staphylococcal Infections - microbiology; Staphylococcus aureus - immunology; Superantigens; Superantigens - immunology; T cell receptors; Virulence factors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-54074-8

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. Bacterial superantigens (sAg) have been shown to induce T cell hyperactivation through cross linking between MHC class II on antigen presenting cells and certain TCRs on T lymphocytes. Here the authors explore how sAg impacts CD4 and CD8 T cell subsets, leading to either expansion or excessive release of pro-inflammatory cytokines and they observe that a temporary state of anergy can occur, while bacterium-specific T cells continue to be generated