Work

Conditional ablation of MHC class I antigen presentation on microglia reduces CD8 T cell accumulation in the CNS in a novel tauopathy animal model 9099

Year: 2025

Type: article

Abstract: Description Tauopathies are a subset of neurological diseases associated with pathologic tau protein accumulation and the formation of neurofibrillary tangles in the brain. There is growing evidence of immune cell infiltration including T cells and an increase of inflammatory microglia in human brains from patients that have Tauopathies. However, the effect of T cells and how they interact with CNS-resident immune cells in these pathologies is not well understood. To answer this question, we developed a neurotropic AAV1 encoding human mutant P301L-Tau. AAV-Tau transduction of neurons in neonatal mice recapitulates features of Tauopathies found in human patients. As microglia are the predominant resident antigen presenting cells within the CNS, we hypothesized that CD8 T cells may be dependent on MHC class I presentation by microglia in mice with Tauopathy to achieve full infiltration and expansion in the brain. To address this hypothesis, we introduced AAV-Tau into our novel transgenic mice for which MHC class I antigen presentation by H-2Kb on microglia can be conditional ablated. We observed lower frequencies of CD8 T cell populations and less CD8 T cell CD69+CD103+ expression in mice with Tauopathy when MHC class I was ablated in microglia. We conclude that microglia class I restricted antigen presentation contributes to the expansion of resident memory CD8 T cells in experimental Tauopathy and therefore are an important driver of the immune response observed in this dementia model. Funding Sources NIH/NINDS: R01NS122174 Mayo Graduate School of Biomedical Sciences Topic Categories Neuroimmunology (NEUR)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.2548