Effect of Superantigen on Detecting Group A Streptococcus Specific T cell responses

Abstract

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), causes a wide variety of clinical manifestations. An effective GAS vaccine would significantly reduce morbidity and mortality, however, development has been restricted by GAS serotype/strain diversity. As GAS is predominantly transmitted through upper respiratory tract infections, a mucosal vaccine may be particularly effective. GAS also produces superantigens which indiscriminately activate immune cells resulting in pathological overactivation of T cells and cytokine release. GAS possesses many superantigen genes, the individual and combined effects of which are unclear.
This project aimed to observe the mucosal T cell response against GAS bacterial culture supernatant as understanding key markers of activation at the mucosal site may aid vaccine development. We evaluated GAS-specific T cell responses from tonsil mononuclear cells (TMNC) which were isolated from human tonsils and donated from the Bristol Royal Hospital for Children and the Bristol Royal Infirmary. Cells were stimulated with bacterial culture supernatants from clinical GAS strains and isogenic superantigen knockout strains. We investigated T cell activation induced markers (AIM) and proliferation as antigen-specific markers of activation. We observed an increase in AIM expression when T cells were cultured with GAS bacterial culture supernatant. The upregulation of AIM and cell proliferation varied between GAS strains and knockout of superantigen, especially of smez, from the bacteria and resulted in a significant decrease in cell proliferation and AIM expression. We also observed generation of memory CD4+ and CD8+ T cells following culture with GAS bacterial culture supernatant.

We conclude that increased proliferation and AIM upregulation are markers of GAS-specific T cell activation, however OX40 may be a more useful marker of activation. We also suggest additional/alternative AIM may provide a more accurate measurement of the GAS-specific response and may identify CD4+ Tfh memory cells.

Date of Award	5 Dec 2023
Original language	English
Awarding Institution	University of Bristol
Supervisor	Anu Goenka (Supervisor)