New study finds excess of T-lymphocytes in the brain of individuals with autism

T-lymphocytes are white blood cells that help to regulate immune functions. While these cells are rarely observed in the brain of healthy, typically developing individuals, they may abound in the brain of those with autism spectrum disorder (ASD), a new study1 suggests.

The study from Beth Israel Deaconess Medical Center and Harvard Medical School, which was led by Marcello Di Stasio and Matthew Anderson, director of the Boston node and clinical neuropathologist for Autism BrainNet, examined the postmortem brains of 25 individuals with ASD and 30 donors without the condition, many of which were acquired through the Autism BrainNet program.

Figure 1: Enlarged lymphocytic cuffs in the ASD brain. Brains of neurotypical individuals (A-B) presented few, sparse lymphocytes (purple dots) around blood vessels, here shown in cross-section as pinkish oval shape. By contrast, brains of individuals with ASD (cases C-D) showed enlarged pockets of lymphocytes around blood vessels. Image adapted from DiStasio M. et al.1

In an article published in the journal Annals of Neurology, DiStasio, Anderson and their colleagues reported that they found a higher number of T-lymphocytes (Figure 1), as well as microscopic, bubble-looking changes in the perivascular CSF space of brain tissue, or ‘blebs,’ in more than half of the ASD cases when compared to those without ASD. The authors suggest that those blebs may have resulted from the T-lymphocytes attacking a particular type of brain cell called ‘astrocytes.’

Figure 2: Greater collagen deposition in ASD brains. Space around blood vessels is enlarged and filled with collagen (green) in the ASD cases (A-C) to a greater degree than cases without the condition (D). Image adapted from DiStasio M. et al.1

Among their many functions, astrocytes provide an interface, or barrier, between the brain tissue and the cerebrospinal fluid and blood vessels. The researchers found enlarged pockets of lymphocytes and ‘blebs’ in the areas of the brain where these barriers (i.e., blood-brain and blood-cerebrospinal fluid) are present, as well as increased deposition of collagen around blood vessels typical of the reaction to the destructive attack by lymphocytes (Figure 2).

Together, these findings suggest an active immune response in ASD brains, though the triggers of this response remain unclear. One possibility is that the excess of lymphocytes reflects a reaction to a viral infection, though the authors screened the brains for several viruses, which turned out to be negative. Alternatively, the changes they observed might reflect an immune attack similar to that seen in autoimmune disorders, such as multiple sclerosis, where the body’s immune system attacks healthy brain cells.

Results from this study are consistent with a growing body of research showing that genes involved in innate immune functions (astroglia, microglia and macrophages) are dysregulated in ASD2,3,4. Here, the researchers established the involvement of the adaptive immune system, specifically T-lymphocytes, within the ASD brain. This study is significant because it finds damage to a particular cell type, the astrocyte, and describes, for the first time, a potential signature of neuropathology in the ASD brain that was unknown before. If replicated, these initial observations could lead to developing potential biomarkers of ASD in living individuals (e.g., blood-based markers) that could be used to improve diagnosis and monitoring of the condition, as well as identifying therapeutic targets.

References

  1. DiStasio M. et al. Ann. Neurology Epub ahead of print (2019) PubMed
  2. Voineagu I. et al.Nature 474, 380-384 (2011) PubMed
  3. Gupta S. et al.Nat. Commun. 5, 5748 (2014) PubMed
  4. Velmeshev D. et al.Science364, 685-689 (2019) PubMed