Theo van den Broek1, Asaf Madi2, Eveline M. Delemarre1, Alvin Schadenberg3,1, Kiki Tesselaar1, José A. M. Borghans1, Stefan Nierkens1, Frank A. Redegeld4, Henny G. Otten1, Maura Rossetti5,6, Salvatore Albani5,6, Rachel Sorek7, Irun R. Cohen2, Nicolaas J. G. Jansen8,9, Femke van Wijk1
1Laboratory of Translational Immunology University Medical Center Utrecht/Wilhelmina Children's Hospital Utrecht The Netherlands
2Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
3Department of Pediatric Intensive Care Bristol Royal Hospital for Children Bristol UK
4Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
5Duke-National University of Singapore Graduate Medical School, Singapore
6SingHealth Translational Immunology and Inflammation Centre SingHealth Singapore
7ImmunArray Ltd., Rehovot, Israel
8Department of Pediatric Cardiothoracic Surgery University Medical Centre Utrecht Utrecht The Netherlands
9Department of Pediatric Intensive Care, University Medical Centre Utrecht, Utrecht, The Netherlands
Tóm tắt
AbstractAn association between T‐cell lymphopenia and autoimmunity has long been proposed, but it remains to be elucidated whether T‐cell lymphopenia affects B‐cell responses to autoantigens. Human neonatal thymectomy (Tx) results in a decrease in T‐cell numbers and we used this model to study the development of autoreactivity. Two cohorts of neonatally thymectomized individuals were examined, a cohort of young (1–5 years post‐Tx, n = 10–27) and older children (>10 years, n = 26), and compared to healthy age‐matched controls. T‐cell and B‐cell subsets were assessed and autoantibody profiling performed. Early post‐Tx, a decrease in T‐cell numbers (2.75 × 109/L vs. 0.71 × 109/L) and an increased proportion of memory T cells (19.72 vs. 57.43%) were observed. The presence of autoantibodies was correlated with an increased proportion of memory T cells in thymectomized children. No differences were seen in percentages of different B‐cell subsets between the groups. The autoantigen microarray showed a skewed autoantibody response after Tx. In the cohort of older individuals, autoantibodies were present in 62% of the thymectomized children, while they were found in only 33% of the healthy controls. Overall, our data suggest that neonatal Tx skews the autoantibody profile. Preferential expansion and preservation of Treg (regulatory T) cell stability and function, may contribute to preventing autoimmune disease development after Tx.
