Eui-Cheol Shin

Shin discovered a pathological significance of bystander T cell activation in human viral disease by studying T cell responses in patients infected with hepatitis A virus (HAV). He found that pre-existing bystander memory CD8+ T cells are unexpectedly activated by cytokines (e.g., IL-15) regardless of their antigen specificity, causing liver cell damage through NKG2D-mediated cytotoxicity.[6] This study demonstrated for that bystander T cells can be a cause of host injury in human viral infection. In subsequent studies, he characterized IL-15-responsive bystander T cells in the liver microenvironment.[7][8][9] In addition, he revealed a mechanism of IL-15 production from epithelial cells[10] and found CD5 as a major negative regulator of IL-15-induced T cell proliferation.[11] His theory about bystander T cell activation has been highlighted as an important pathological mechanism in human viral disease.[12]

During the COVID-19 pandemic, Shin studied immune responses to COVID-19. First, he revealed a mechanism of hyper-inflammation in patients with severe COVID-19 by performing single-cell RNA-seq analysis.[13] In his study, he reported a paradoxical role of type I IFNs in exacerbating inflammation in COVID-19 patients.[14] He also performed a detailed characterization of SARS-CoV-2-specific CD8+ T cells, revealing that despite expressing PD-1, they are functionally active and not exhausted.[15] These findings corrected the misinformation that had been previously reported during the early stages of the COVID-19 pandemic. This was one of the first studies that detected SARS-CoV-2-specific CD8+ T cells using MHC class I multimers. In addition, he demonstrated that SARS-CoV-2-specific T cell memory is sustained for a long period after recovery from COVID-19 with the successful development of stem cell-like memory T cells.[16] Moreover, he showed that memory T cells elicited by COVID-19 mRNA vaccination substantially respond to the Omicron variant.[17] On the basis of his findings, he proposed T cell-oriented strategies for controlling the COVID-19 pandemic.[18]

• Kim, J., Chang, D. Y., Lee, H. W., Lee, H., Kim, J. H., Sung, P. S., ... & Shin, E. C. (2018). Innate-like cytotoxic function of bystander-activated CD8+ T cells is associated with liver injury in acute hepatitis A. Immunity, 48(1), 161–173.
• Lee, J. S., Park, S., Jeong, H. W., Ahn, J. Y., Choi, S. J., Lee, H., ... & Shin, E. C. (2020). Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Science immunology, 5(49), eabd1554.
• Rha, M. S., Jeong, H. W., Ko, J. H., Choi, S. J., Seo, I. H., Lee, J. S., ... & Shin, E. C. (2021). PD-1-expressing SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional in patients with COVID-19. Immunity, 54(1), 44–52.
• Noh, J. Y., Jeong, H. W., Kim, J. H., & Shin, E. C. (2021). T cell-oriented strategies for controlling the COVID-19 pandemic. Nature Reviews Immunology, 21(11), 687–688.
• Koh, J. Y., Rha, M. S., Choi, S. J., Lee, H. S., Han, J. W., Nam, H., ... & Shin, E. C. (2022). Identification of a distinct NK-like hepatic T-cell population activated by NKG2C in a TCR-independent manner. Journal of hepatology, 77(4), 1059–1070.
• Jung, M. K., Jeong, S. D., Noh, J. Y., Kim, D. U., Jung, S., Song, J. Y., ... & Shin, E. C. (2022). BNT162b2-induced memory T cells respond to the Omicron variant with preserved polyfunctionality. Nature Microbiology, 7(6), 909–917.