Neutrophil deficiency increases T cell numbers at the site of tissue injury in mice.

Abstract

During the investigation of muscle injury and regeneration in neutrophil-deficient mice, we observed unexpected changes in the cellular composition of tissue-infiltrating inflammatory cells. Neutrophil deficiency led to reduced macrophage infiltration and a striking increase in nonconventional CD4^- CD8^- (double-negative) αβ and γδ T cell numbers, peaking at Day 3 postinjury. In exploring the underlying mechanisms, we identified previously unrecognized cellular and tissue alterations, including bone marrow erythroid insufficiency and compensatory extramedullary hematopoiesis accompanied by splenomegaly. Using a thioglycolate-induced peritonitis model, we further demonstrated that elevated T-cell numbers reflect a general inflammatory response in neutrophil-deficient mice. Our findings suggest that this model provides a valuable platform for investigating the properties and functions of rare nonconventional T cells in tissue injury and diverse inflammatory conditions. Impact statement Our studies demonstrate that neutrophil-deficient mice may provide a valuable model for investigating the roles and characteristics of non-conventional T cells in tissue inflammation and repair.