5 years ago

Human neonatal thymectomy induces altered B-cell responses and autoreactivity

Human neonatal thymectomy induces altered B-cell responses and autoreactivity
Kiki Tesselaar, Irun R. Cohen, José A. M. Borghans, Salvatore Albani, Nicolaas J. G. Jansen, Rachel Sorek, Maura Rossetti, Femke Wijk, Theo den Broek, Eveline M. Delemarre, Stefan Nierkens, Alvin W. L. Schadenberg, Frank A. Redegeld, Asaf Madi, Henny G. Otten
An 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. Neonatal Tx results in T-cell lymphopenia with subsequent homeostatic T-cell proliferation and memory T-cell expansion, but an unaltered B-cell phenotype. The antibody repertoire is skewed toward autoreactivity following memory T-cell expansion. Preferential expansion of regulatory T cells might prevent autoreactivity from developing into autoimmune disease.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201746971

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