Details

Autor(en) / Beteiligte

• Humblin, Etienne
• Korpas, Isabel
• Lu, Jiahua
• Filipescu, Dan
• van der Heide, Verena
• Goldstein, Simon
• Vaidya, Abishek
• Soares-Schanoski, Alessandra
• Casati, Beatrice
• Selvan, Myvizhi E
• Gümüş, Zeynep H
• Wieland, Andreas
• Corrado, Mauro
• Cohen-Gould, Leona
• Bernstein, Emily
• Homann, Dirk
• Chipuk, Jerry
• Kamphorst, Alice O

Titel

Sustained CD28 costimulation is required for self-renewal and differentiation of TCF-1 + PD-1 + CD8 T cells

Ist Teil von

• Science immunology, 2023-08, Vol.8 (86), p.eadg0878

Ort / Verlag

United States

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• During persistent antigen stimulation, such as in chronic infections and cancer, CD8 T cells differentiate into a hypofunctional programmed death protein 1-positive (PD-1 ) exhausted state. Exhausted CD8 T cell responses are maintained by precursors (Tpex) that express the transcription factor T cell factor 1 (TCF-1) and high levels of the costimulatory molecule CD28. Here, we demonstrate that sustained CD28 costimulation is required for maintenance of antiviral T cells during chronic infection. Low-level CD28 engagement preserved mitochondrial fitness and self-renewal of Tpex, whereas stronger CD28 signaling enhanced glycolysis and promoted Tpex differentiation into TCF-1 exhausted CD8 T cells (Tex). Furthermore, enhanced differentiation by CD28 engagement did not reduce the Tpex pool. Together, these findings demonstrate that continuous CD28 engagement is needed to sustain PD-1 CD8 T cells and suggest that increasing CD28 signaling promotes Tpex differentiation into more functional effector-like Tex, possibly without compromising long-term responses.