Oligoclonal expansion of atypical Vδ2- γδ T cells in Good's Syndrome

Abstract

Good’ssyndromeisarareadult-onsetimmunodeficiency characterized by thymoma, hypogammaglobulinemia, B-cell lymphopenia, and T-cell dysfunction. Despite well-characterized defects in conventional immune subsets, the impact of this disorder on unconventional Tcells, including γδ Tcells, remains largely unexplored. In this study, we analyse γδ T cells in 10 patients with Good’s syndrome using immunophenotyping, functional assays, and T-cell receptor (TCR)δ repertoire profiling of peripheral blood and thymoma tissue. Our analyses reveal a pronounced expansion of the Vδ2⁻ γδ T-cell compartment, composed primarily of Vδ1⁺,Vδ3⁺ and the exceptionally rare Vδ8⁺ subsets. The Vδ2⁻ cells are characterized by an activated and effector phenotype and a private and oligoclonal TCRδ repertoire. The thymoma tissue contains distinct clonotypes compared to circulation, suggesting clonal focusing in response to the tumor. Together, our findings show that γδ T-cell perturbations are integral characteristics of Good’s syndrome and broaden our understanding of immune dysregulation in this acquired immunodeficiency.