GSBMS Date 2024-01-16 오전 10:09:30 Inquiries 235
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)