Dopamine-2 Receptor Induces T Cell Activation in Children with Movement and Psychiatric Disorders   — Australasian Cytometry Society
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Dopamine-2 Receptor Induces T Cell Activation in Children with Movement and Psychiatric Disorders   (24113)

Deepti Pilli 1 , Sudarshini Ramanathan 1 , Nese Sinmaz 1 , Fiona Tea 1 , Anthony D Kelleher 2 , Tina K Nguyen 1 , Alicia Zou 1 , Vera Merheb 1 , Russell C Dale 1 , Fabienne Brilot 1
  1. Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children’s Hospital at Westmead, Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Westmead, NSW, Australia
  2. The Kirby Institute for Infection and Immunity in Society, UNSW Australia, Sydney, NSW, Australia; St Vincent's Hospital, Sydney, NSW, Australia

Introduction and Aim: With the growing number of autoantibodies that target brain antigens, such as the dopamine-2 receptor (D2R), an autoimmune aetiology has been proposed in a subgroup of movement and psychiatric disorders. As anti-D2R antibodies in paediatric patients are immunoglobulin G, it is postulated that autoantibody-producing B cells have undergone isotype switching via interactions with D2R-autoreactive T cells. However, these T cells remain unexplored. Hence, we aim to identify and characterise D2R-autoreactive T cells in children with movement and psychiatric disorders.

Methods: A highly sensitive whole blood flow cytometry assay was used to detect rare antigen-specific T cells. Co-expression of CD25 and CD134 on CD4+ T cells was assessed in patients (n=18) and controls (n=16) following stimulation with a library of 67 synthetic human D2R 15-mer peptides and positive controls, PHA, SEB and tetanus toxoid (TT). Patients with a frequency of activated CD4+ T cells greater than 4 standard deviations above the control mean was considered D2R-reactive.

Results: The percentage of activated CD4+CD25+CD134+ T cells was higher in some patients in response to D2R peptides encompassing aa51-75 (1/18), aa121-155 (2/18), aa156-195 (2/18), aa206-265 (1/18), and aa381-443 (1/18). The remaining peptides did not elicit a notable activation in patients nor controls. When stimulated by PHA, SEB and TT, percentage of CD4+CD25+CD134+ T cells were similar in both cohorts.

Conclusion: A subgroup of paediatric patients with movement and psychiatric disorders exhibit an amplified activation of D2R-specific CD4+ T cells. Characterising autoreactive T cells in autoimmune-associated disorders can offer wider options for immunotherapies.

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