T-cell receptor diversity is selectively skewed in T-cell populations of patients with Wiskott-Aldrich syndrome

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Wiskott-Aldrich syndrome (WAS) is a severe disorder characterized by thrombocytopenia, eczema, immunodeficiency, and increased risk of autoimmune disease and lymphoid malignancies. The immunodeficiency caused by a lack of WAS protein expression has been mainly attributed to defective T-cell functions. WhetherWASmutations differentially influence the T-cell receptor (TCR) diversity of different T-cell subsets is unknown.


We aimed to identify the degree and pattern of skewing in the variable region of the TCR β-chain (Vβ) in different T-cell subsets from patients with WAS.


The TCR repertoire diversity in total peripheral T cells, sorted CD4+ and CD8+ T cells, and CD45RA+ (CD45RA+CD45RO− cells) and CD45RO+ (CD45RA−CD45RO+ cells) CD4+ and CD8+ T cells from patients with WAS and age-matched healthy control subjects was analyzed and compared by using spectratyping of complementarity-determining region 3. The complementarity-determining region 3 of TCRβ transcripts in CD45RA+CD4+ and CD45RA+CD8+ T cells, CD45RO+CD4+ T cells, CD8+ terminally differentiated effector memory T (Temra) cells, and naive CD8+ T cells (CD8+CD45RO−CCR7+ cells) from patients and control subjects were analyzed and compared by using high-throughput sequencing.


The TCR repertoire diversity in CD45RO+CD4+ T cells and CD8+ Temra cells of patients with WAS was significantly skewed in comparison with that seen in age-matched control subjects.


Our results indicate thatWASgene mutations selectively influence TCR repertoire development or expansion in CD45RO+ (memory) CD4+ T cells.

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