T-lymphocytes target astrocytes in the postmortem autism brain

Although published studies of postmortem brains have implicated patterns of gene expression and cell types involved in the innate immune system as being associated with autism spectrum disorder (ASD) neuropathology, our understanding of neuroimmune functions in the disorder is far from complete. A new study now suggests the possible role of the T-lymphocytes of the adaptive immune system in ASD.

The new work was led by Matthew Anderson, director of the Boston node of Autism BrainNet. Anderson and colleagues examined the postmortem brains of 25 individuals with ASD and 30 individuals without ASD, many of which were acquired through the Autism BrainNet program. They reported a higher number of T-lymphocytes, as well as microscopic blebs in the perivascular space, in the brains of individuals with ASD compared to individuals without ASD. These blebs, which were commonly associated with astrocytes, are signs of cell injury and raise the possibility that there is an active immune response in the ASD brain that targets astrocytes.

This is the first time that such a neuropathological signature has been reported in ASD postmortem brain. In the absence of evidence for a particular infection, the authors suggest that the changes might reflect an autoimmune response. Pending replication in another set of postmortem brains, the data hold out the prospect of a blood-based biomarker that could be used to improve diagnosis and monitoring of living individuals with ASD.

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Increased number of perivascular T-lymphocytes in ASD postmortem brain. Perivascular T-lymphocyte counts in up to 16 vessels identified by visual inspection showed an increase in the brain of individuals with ASD compared to individuals without ASD. The aggregate difference between cases with and without ASD was statistically significant. Image from DiStasio M.M. et al. (2019).


T-lymphocytes and cytotoxic astrocyte blebs correlate across autism brains.

DiStasio M.M, Nagakura I., Nadler M.J., Anderson M.

Ann. Neurol. 88, 885-898 (November 30, 2019) PubMed

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