Oligoclonal expansion of atypical Vdelta2(-) gammadelta T cells in Good&#39;s Syndrome

Bandala-Sanchez, E; Fuentes-Antras, J; Scolamiero, L; Chatelier, J; Ramsay, KA; Morey, A; Tsang, S; Forde, M; Bosco, JJ; Pumar, M; Sanchez-Ramon, S; Guevara-Hoyer, K; Godsell, J; Spriggs, K; von Borstel, A; Chan, S; Howson, LJ

Oligoclonal expansion of atypical Vdelta2(-) gammadelta T cells in Good's Syndrome

Author(s): Bandala-Sanchez, E; Fuentes-Antras, J; Scolamiero, L; Chatelier, J; Ramsay, KA; Morey, A; Tsang, S; Forde, M; Bosco, JJ; Pumar, M; Sanchez-Ramon, S; Guevara-Hoyer, K; Godsell, J; Spriggs, K; von Borstel, A; Chan, S; Howson, LJ;
Journal Title: Nature Communications
Abstract: Good's syndrome is a rare adult-onset immunodeficiency 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 T cells, including gammadelta T cells, remains largely unexplored. In this study, we analyse gammadelta T cells in 10 patients with Good's syndrome using immunophenotyping, functional assays, and T-cell receptor (TCR)delta repertoire profiling of peripheral blood and thymoma tissue. Our analyses reveal a pronounced expansion of the Vdelta2(-) gammadelta T-cell compartment, composed primarily of Vdelta1(+), Vdelta3(+) and the exceptionally rare Vdelta8(+) subsets. The Vdelta2(-) cells are characterized by an activated and effector phenotype and a private and oligoclonal TCRdelta repertoire. The thymoma tissue contains distinct clonotypes compared to circulation, suggesting clonal focusing in response to the tumor. Together, our findings show that gammadelta T-cell perturbations are integral characteristics of Good's syndrome and broaden our understanding of immune dysregulation in this acquired immunodeficiency.
Publisher: Springer Nature
Keywords: Humans; *Receptors, Antigen, T-Cell, gamma-delta/immunology/metabolism/genetics; *Thymoma/immunology/pathology; Female; Male; Adult; Middle Aged; Thymus Neoplasms/immunology; Immunophenotyping; *Agammaglobulinemia/immunology/genetics; *Immunologic Deficiency Syndromes/immunology/genetics; *T-Lymphocytes/immunology; *T-Lymphocyte Subsets/immunology; Lymphopenia/immunology
Research Division(s): Immunology
PubMed ID: 42277046
Publisher's Version: https://doi.org/10.1038/s41467-026-74273-9
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-026-74273-9
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-06-19 01:23:32

Last Modified: 2026-08-14 11:30:41