γδ T Cells and Inborn Errors of Immunity

Abstract

Gamma delta (γδ) T cells are pivotal in diverse immune responses, encompassing defense against infections, cancer surveillance, and tissue repair. Inborn errors of immunity (IEI) are rare genetic conditions disrupting human immune system development and function, with some impacting γδ T cells. In this review, we focus on IEI leading to a relative increase or decrease of γδ T cells compared to αβ T cells. We discuss how these disorders provide unique insights, in particular concerning the importance of signaling pathways for human αβ versus γδ T cell development, function, and homeostasis. Wherever suitable, we also include data from respective mouse models of IEIs that corroborate patient observations but also illustrate relevant species differences. This comparative approach identifies gaps in knowledge and defines areas for future research. Overall, this review underscores the relevance of IEIs in elucidating the development and function of human γδ T cells with potential implications for diagnosing and treating patients with immune disorders.

Keywords: human; inborn errors of immunity; mouse; primary immunodeficiency; γδ T cells.

FIGURE 1

Summary of human genetic conditions associated with an altered balance between αβ and γδ T cells. * indicates genes in which hypomorphic, but not null mutations have been associated with γδ T cell predominance. + indicates genes in which mutations have been associated with γδ predominance only in a few patients.