Work

KLF2 couples differentiation and migration of CD8 T cells during chronic viral infection and cancer 2390

Year: 2025

Type: article

Abstract: Description During chronic viral infection and cancer, differentiation of CD8 T cells into various exhausted T cell subsets is tightly controlled by transcription factors. Among exhausted T cells, there is an effector-like CD8 T cells subset with greater cytotoxic effector function. However, the transcriptional program controlling the differentiation of effector-like CD8 T cells is incompletely understood. Here, using joint single-cell profiling of the transcriptome and epigenome of CAR T cells, we established the gene regulatory network (GRN) of effector-like CAR T cells. Transcription factor KLF2 was one of the hub transcription factors in the effector-like GRN. Loss of KLF2 significantly diminished the effector-like CD8 subset in both CAR T cells and antiviral CD8 T cells. In the spleen, KLF2 deficient CD8 T cells upregulated the gene signature of terminal exhaustion, suggesting a role of KLF2 in regulating the bifurcation of exhaustion versus effector-like cell fates. In both chronic viral infection and cancer, KLF2 deficiency impaired CD8 T cell infiltration to non-lymphoid tissues. Thus, during chronic antigen stimulation, KLF2 simultaneously regulates differentiation and migration of exhausted CD8 T cells. Funding Sources R21AG083398, R01AI158294, R01AI158294-03S1, CRI4287 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.315

Authors: Tuoqi Wu, Chen Yao, Ziang Zhu

Institutions: Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W4416446232