Human neonatal thymectomy induces altered B-cell responses and auto-reactivity

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 auto-antigens. Human neonatal thymectomy results in a decrease in T-cell numbers and we used this model to study the development of auto-reactivity. Two cohorts of neonatally thymectomized individuals were examined, a cohort of young (1-5 years post-thymectomy, n = 10-27) and older children (>10years,n = 26), and compared to healthy age-matched controls. T- and B-cell subsets were assessed and auto-antibody profiling performed. Early post-thymectomy, a decrease in T-cell numbers (2.75 × 10^{^9}/L vs. 0.71 × 10^{^9}/L) and an increased proportion of memory T-cells (19.72% vs. 57.43%) were observed. The presence of auto-antibodies 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 auto-antigen microarray showed a skewed auto-antibody response after thymectomy. In the cohort of older individuals, auto-antibodies 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 thymectomy skews the auto-antibody profile. Preferential expansion and preservation of Treg (regulatory T) cell stability and function, may contribute to preventing autoimmune disease development after thymectomy.

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