PhD Student University of Liverpool Liverpool, England, United Kingdom
Abstract Text:
Introduction: Green Tea, derived from the Camellia sinensis plant, is a common constituent of herbal supplements. Green Tea extracts (GTE) have been linked with immune-mediated liver injury and associated with the expression of HLA-B*35:01. Epigallocathecin-3-O-gallate (EGCG) is the most abundant catechin found in GTE and is implicated in liver injury. The aim of this study was to investigate the immunogenicity of EGCG in healthy donors positive and negative for the HLA-B*35:01 risk allele.
Methods: PBMC and T-cell priming assays using cells from HLA-B*35:01 positive and negative healthy donors (n=4) were undertaken to assess EGCG’s ability to prime naïve individuals, with and without immune checkpoint blockade. EGCG-responsive T-cell clones (TCC) were generated via repetitive mitogen stimulation examined for specificity, phenotype, cytokine secretion and pathways of T-cell activation.
Results: Significant proliferative responses were identified in PBMC from 2/4 allele positive and 2/4 negative donors. EGCG-specific priming of T-cells was observed in the presence of PD-1 and PD-L1 blockade. A number of EGCG-specific TCCs were identified from healthy donors expressing HLA-B*35:01. TCCs proliferated in a dose-dependent manner and secreted IFNγ, IL-5, IL-13 and Granzyme B. TCC had a CD4+ phenotype, with activation restricted to MHC Class II.
Conclusion: These findings suggest EGCG has an intrinsic ability to be immunogenic and can effectively prime naïve T-cells from HLA-B*35:01 positive and negative donors. Blockade of co-inhibitory signalling pathways potentiates the priming seen. EGCG is able to activate CD4+ TCC, stimulating the release of pro-inflammatory and cytolytic cytokines, driven through MHC Class II interactions.
