Perinatal thymic-derived CD8αβ-expressing γδ T cells are innate IFN-γ producers that expand in IL-7R-STAT5B-driven neoplasms.

The contribution of γδ T cells to immune responses is associated with
rapid secretion of interferon-γ (IFN-γ). 这里, 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.