Author(s):
Sumaria, Nital ; Fiala, Gina ; Inácio, Daniel ; Curado Avelar, Marta Maria ; Cachucho, Ana ; Pinheiro, Rúben ; Wiesheu, Robert ; Kimura, Shunsuke ; Courtois, Lucien ; Blankenhaus, Birte ; Darrigues, Julie ; Suske, Tobias ; Almeida, Afonso ; Minguet, Susana ; Asnafi, Vahid ; Lhermitte, Ludovic ; Mullighan, Charles G. ; Coffelt, Seth B. ; Moriggl, Richard ; Barata, João T. ; Pennington, Daniel J. ; Silva-Santos, Bruno
Date: 2024
Persistent ID: http://hdl.handle.net/10451/65466
Origin: Repositório da Universidade de Lisboa
Description
The contribution of γδ T cells to immune responses is associated with rapid secretion of interferon-γ (IFN-γ). Here, we show a perinatal thymic wave of innate IFN-γ-producing γδ T cells that express CD8αβ heterodimers and expand in preclinical models of infection and cancer. Optimal CD8αβ+ γδ T cell development is directed by low T cell receptor signaling and through provision of interleukin (IL)-4 and IL-7. This population is pathologically relevant as overactive, or constitutive, IL-7R-STAT5B signaling promotes a supraphysiological accumulation of CD8αβ+ γδ T cells in the thymus and peripheral lymphoid organs in two mouse models of T cell neoplasia. Likewise, CD8αβ+ γδ T cells define a distinct subset of human T cell acute lymphoblastic leukemia pediatric patients. This work characterizes the normal and malignant development of CD8αβ+ γδ T cells that are enriched in early life and contribute to innate IFN-γ responses to infection and cancer.
