Patients with CD3G mutations reveal a role for human CD3? in Treg diversity and suppressive function

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dc.contributor.authorRowe, Jared H.
dc.contributor.authorDelmonte, Ottavia M.
dc.contributor.authorKeles, Sevgi
dc.contributor.authorStadinski, Brian D.
dc.contributor.authorDobbs, Adam K.
dc.contributor.authorHenderson, Lauren A.
dc.contributor.authorYamazaki, Yasuhiro
dc.date.accessioned2024-02-23T14:27:12Z
dc.date.available2024-02-23T14:27:12Z
dc.date.issued2018
dc.departmentNEÜen_US
dc.description.abstractIntegrity of the T-cell receptor/CD3 complex is crucial for positive and negative selection of T cells in the thymus and for effector and regulatory functions of peripheral T lymphocytes. In humans, CD3D, CD3E, and CD3Z gene defects are a cause of severe immune deficiency and present early in life with increased susceptibility to infections. By contrast, CD3G mutations lead to milder phenotypes, mainly characterized by autoimmunity. However, the role of CD3 gamma in establishing and maintaining immune tolerance has not been elucidated. In this manuscript, we aimed to investigate abnormalities of T-cell repertoire and function in patients with genetic defects in CD3G associated with autoimmunity. High throughput sequencing was used to study composition and diversity of the T-cell receptor beta (TRB) repertoire in regulatory T cells (T(reg)s), conventional CD4(+) (T-conv), and CD8(+) T cells from 6 patients with CD3G mutations and healthy controls. T-reg function was assessed by studying its ability to suppress proliferation of T-conv cells. T-reg cells of patients with CD3G defects had reduced diversity, increased clonality, and reduced suppressive function. The TRB repertoire of T-conv cells from patients with CD3G deficiency was enriched for hydrophobic amino acids at positions 6 and 7 of the CDR3, a biomarker of self-reactivity. These data demonstrate that the T-cell repertoire of patients with CD3G mutations is characterized by a molecular signature that may contribute to the increased rate of autoimmunity associated with this condition.en_US
dc.description.sponsorshipDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Healthen_US
dc.description.sponsorshipThis work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.en_US
dc.identifier.doi10.1182/blood-2018-02-835561
dc.identifier.endpage2344en_US
dc.identifier.issn0006-4971
dc.identifier.issn1528-0020
dc.identifier.issue21en_US
dc.identifier.pmid29653965en_US
dc.identifier.scopus2-s2.0-85047878016en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage2335en_US
dc.identifier.urihttps://doi.org/10.1182/blood-2018-02-835561
dc.identifier.urihttps://hdl.handle.net/20.500.12452/14488
dc.identifier.volume131en_US
dc.identifier.wosWOS:000433142600011en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Soc Hematologyen_US
dc.relation.ispartofBlooden_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[Keyword Not Available]en_US
dc.titlePatients with CD3G mutations reveal a role for human CD3? in Treg diversity and suppressive functionen_US
dc.typeArticleen_US

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