Increased caspase activity primes human lyme arthritis synovial γδ T cells for proliferation and death (160.11)

Abstract

Abstract γδ T cells function between the innate and adaptive immune responses, promoting antigen-presenting cell function, presenting antigen, and manifesting cytolytic activity. Their numbers increase in infections, such as HIV, and at sites of chronic inflammation. However, the turnover dynamics of human γδ T cells are poorly understood. Here we find that despite more rapid proliferation, human Lyme arthritis synovial γδ T cells of the Vδ1 subset have reduced cell number expansion in vitro compared to αβ T cells due to increased cell death by the γδ T cells. Because caspases are involved in cell proliferation and death, and signaling is more efficient through the γδ-TCR than the αβ-TCR, we examined active caspases during cell cycling and following TCR restimulation. We observed higher overall caspase activity in Borrelia-reactive γδ T cells than comparable αβ T cells. This was paralleled by greater spontaneous and TCR restimulation-induced cell death of the γδ T cells. Furthermore, the transition from cell growth to death was associated with a transition of active caspases from the cell membrane to the cytoplasm. Our current findings thus are consistent with a model where human γδ T cells evolved to function quickly and transiently, in an innate fashion.