Objectives: Based on our previous reports of gene expression in autism and altered immune cell function, we sought to establish whether CD8+ T cells have abnormal phenotypes and function in autism.
Methods: Peripheral blood mononuclear cells (PBMC) from 16 children with autism and 16 typically developing children between the ages of 2 and 5 years were obtained by density gradient centrifugation. Dynamic cell function was determined by stimulation of PBMC with PMA/ionomycin for 24 hours. Supernatants were collected and analyzed for cytokine production by luminex analysis. Phenotypic analysis of CD8+ T cells were performed by flow cytometry.
Results: The percent of CD8+ T cells that contained the cytolytic proteins, perforin and granzyme B were increased in unstimulated cell cultures from children with autism compared to controls (p < 0.004). Following stimulation the number of CD8+ T cells containing cytolytic proteins increased significantly in controls but decreased in children with autism (p < 0.01). In addition, following stimulation, surface expression of CD107a, a marker of granule release, was decreased in children with autism compared to controls (p <0.003), suggesting that activation and release of cytolytic proteins due to stimulation was altered in autism compared to controls. Intracellular staining of the inflammatory cytokine interleukin-6 (IL-6) in CD8+ T cells was increased at resting levels in children with autism compared to controls (p = 0.03). However, following stimulation intracellular IL-6 and interferon gamma (IFNg) were increased significantly in controls but decreased in children with autism (p < 0.01), possibly suggesting an “exhausted” or “maximized” cellular response.
Conclusions: These studies point to specific CD8+ T cell function abnormalities in the blood of individuals with autism. Abnormal CD8+ T cell function may represent an important link between inflammatory processes that have reported in some children with autism, and could point to a specific immune basis for the disorder in many subjects.