SUNGKYUNKWAN UNIVERSITY SCHOOL OF MEDICINE

Prof. Se Jin Lim (Department of Immunology, Division of Basic Medical Sciences) and colleagues have identified a TCF1-expressing CD8 T-cell population that is key to maintaining T-cell responses in a model of acute GvHD induction by allogeneic hematopoietic stem cell transplantation.

Graft-versus-host disease (GvHD) is a serious complication that occurs in blood stem cell transplant patients and is caused by the donors immune cells, especially T cells, recognizing the recipients tissues as foreign antigens, activating and attacking them.

In this study, the research team hypothesized that chronic viral infection, tumor microenvironment, and T-cell differentiation would be similar from the donors immune cell perspective due to the constant stimulation of donor antigens. Using an acute GvHD model with allogeneic transplantation, we found that donor-derived activated T cells consist of a progenitor cell population expressing the transcriptional regulator TCF1 and an effector cell population expressing Tim-3. We found that TCF1-expressing CD8 T cells lack cytolytic capacity but can proliferate exclusively after antigen stimulation and play a key role in maintaining GvHD symptoms as they differentiate into Tim-3-expressing effector T cells with cytolytic capacity upon proliferation. Furthermore, the TCF1-expressing CD8 T cell population is predominantly present in the spleen and exhibits resident characteristics.

Furthermore, the same CD8 T-cell differentiation phenotype was confirmed using a xenogeneic transplantation model of acute GvHD, demonstrating that human T cells differentiate in the same way.

"The discovery of these isotypes of allogeneic activated T cells may have important implications for the development of immunotherapy strategies for acute GvHD," said Prof. Se Jin Lim.

The research was supported by the National Research Foundation of Korea (NRF), the Biomedical Technology Development Project, and the National Cancer Centers Public Interest Cancer Research Project, and was published on September 22 in the international journal Nature Communications (IF: 17.694).

In vivo proliferation and differentiation capacity of TCF1-expressing progenitor cells in an acute GvHD model 

(Source: Lee S and Lee K et al. (2023) Nat Comm)

Title: Defining a TCF1-expressing progenitor allogeneic CD8+ T cell subset in acute graft-versus-host disease (Nature Communications)

Authors: Se jin Lim (Corresponding author), Solhui Lee, and Eunhee Lee (Co-first author)