Dissecting the regulatory network of transcription factors in T cell phenotype/functioning during GVHD and GVT

Abstract

Transcription factors play a major role in regulation and orchestration of immune responses. The immunological context of the response can alter the regulatory networks required for proper functioning. While these networks have been well-studied in canonical immune contexts like infection, the transcription factor landscape during alloactivation remains unclear. This review addresses how transcription factors contribute to the functioning of mature alloactivated T cells. This review will also examine how these factors form a regulatory network to control alloresponses, with a focus specifically on those factors expressed by and controlling activity of T cells of the various subsets involved in graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) responses.

Keywords: GVHD; GVL; allotransplantation; regulatory networks; transcription factors.

Figure 1

Major Functions of Alloactivated T cells. When alloreactive T cells recognize alloantigen (recipient self antigen) presented by an antigen presenting cell (APC), the T cell becomes alloactivated. These T cells then perform a variety of functions, including: proliferate, differentiate into cytotoxic cells, produce cytokines and cytotoxic mediators, migrate, become exhausted, survive or undergo apoptosis, and express altered gene programs. These T cell functions lead to graft-versus-host disease (GVHD), which damages healthy host tissues in the target organs (skin, small intestine, liver). These T cell functions also lead to the graft-versus-tumor (GVT, also called graft-versus-leukemia, GVL) effect, which eliminates residual malignant cells. Figure created using BioRender.com.

Figure 2

Summary Model - Transcriptional Control of GVHD and GVT. Numerous transcription factors have an impact on T cell function during alloactivation. Alterations in these factors leads to changes in GVHD and/or GVT outcomes. Shown here is the contribution of each factor discussed to each of the major T cell functions, as well as the factor’s role in GVHD (damaging or protective) and GVT (dispensable or critical). Figure created using BioRender.com.