87. T cell malfunction and a pro-inflammatory skew in autism spectrum disorders

Abstract

Immune dysfunction is evident in many cases of autism spectrum disorders (ASD). Elevated levels of pro-inflammatory molecules, a deficiency and malfunction of T cells, and activated microglia in brain were detected in ASD. Whether a pro-inflammatory skew can cause ASD is unclear, but mounting evidence suggests that maternal immune activation (MIA) may contribute to the development of autistic features. MIA causes autistic-like behavioral deficits in offspring that can be prevented in mice by replacing their immune systems via bone marrow transplantation. We have identified that meningeal T cells, surrounding the brain, are necessary for normal brain function. Here we tested if malfunctioning T cells underlie behavioral dysfunction in ASD. We used multiple approaches to first deplete T cells in adult mice, and then assessed their behavior. We found that mice deficient or depleted of T cells have autistic-like dysfunction in multiple cognitive and social behavioral assays as well as an overall pro-inflammatory skew of their innate compartment (myeloid cells in the meninges and microglia). These data demonstrate that T cell malfunction in mice may be used to model behavioral abnormalities associated with ASD. We propose that in some cases of ASD, T cell malfunction leads to an unregulated pool of meningeal myeloid cells and microglia. This unleashes a pro-inflammatory environment that results in neuronal dysfunction and ultimately behavioral deficits in autism.