Eomesodermin(+) CD4(+) T 细胞对治愈性免疫治疗结局至关重要

Interleukin 10 (IL-10)-producing CD4 + type-1 regulatory T cells (Tr1) promote immune tolerance during chronic infection, autoimmunity, and transplantation.

However, specific Eomesodermin (Eomes)-dependent stages of Tr1 differentiation and function remain unclear. Using preclinical models of bone marrow transplantation (BMT), we demonstrated a Tr1 differentiation trajectory in vivo from Eomes + IL-10 - to Eomes + IL-10 + subsets with the acquisition of cytokine, cytolytic, and exhaustion features. The Eomes + CD4 + fraction represented the dominant cytotoxic subset after BMT, mediating graft-versus-leukemia effects while limiting inflammation.

In CD19-targeted chimeric antigen receptor (CAR) T cell immunotherapy, Eomes drove the same CD4 + Tr1 phenotype that controlled cytolysis, while mitigating immune toxicity and promoting persistence.

In individuals with high-grade B cell lymphomas that had long-term disease control after receiving commercial CD19-targeted CAR T cells, Eomes + Tr1 cells represented a stable population comprising 40%-80% of the CD4 + CAR T cell population. Hence, Eomes controls both regulatory and cytotoxic programs in CD4 + T cells, essential for curative immunotherapy outcomes.