RT Journal Article
SR Electronic
T1 TCF-1 in CD8 T cells separates GVHD from GVL
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.22.436494
DO 10.1101/2021.03.22.436494
A1 Rebecca Harris
A1 Mahinbanu Mammadli
A1 Adriana May
A1 Qi Yang
A1 Ivan Ting Hin Fung
A1 Jyoti Misra Sen
A1 Mobin Karimi
YR 2021
UL http://biorxiv.org/content/early/2021/03/23/2021.03.22.436494.abstract
AB Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for hematological malignancy due to graft-versus-leukemia (GVL) effects, mediated by alloreactive donor T cells. However, these same donor cells cause graft-versus-host disease (GVHD), a life-threatening complication. During GVHD, donor T cells proliferate, migrate, and produce cytokines, leading to damage of healthy host tissues. Separating the linked processes of GVHD and GVL is critical to improving outcomes. Here we show that TCF-1, a major T cell developmental factor, plays a role in regulation of these processes. Using a mouse model of allo-HSCT leading to GVHD, we found that conditional loss of TCF-1 in mature CD8 T cells separates GVHD from GVL, providing an optimal clinical phenotype. This occurred due to changes in cytokine production, proliferation, cell survival, chemokine receptor expression, and gene expression. Thus, modulation of TCF-1 signaling reduces GVHD severity and persistence, but maintains GVL effects, and could be useful for allo-HSCT or other T cell-mediated disorders. Furthermore, here and in our companion manuscript we show that regulation of mature, alloactivated T cells by TCF-1 differs between CD4 and CD8 T cells, suggesting that TCF-1 is critical for regulation of mature alloactivated T cells, with unique programs in each subset.Competing Interest StatementThe authors have declared no competing interest.