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| Home > Publications database > Expansion of a distinct cytotoxic CD4 TFH-cell cluster in lymph nodes of patients with complicated Common Variable Immunodeficiency. |
| Journal Article | DKFZ-2025-02653 |
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2025
Elsevier
Amsterdam [u.a.]
Abstract: Patients with common variable immunodeficiency (CVID) suffer from hypogammaglobulinemia linked to an inadequate differentiation of long-lived humoral immunity and an impaired germinal center (GC) response in the majority of cases.To further characterize the transcriptome and phenotype of T follicular helper (TFH) cells of complicated CVID (CVIDc) patients as key players in the GC reaction.Sorted TFH cells from CVIDc lymph nodes and non-CVID immunocompetent tonsils were analyzed by bulk-RNA-sequencing. Altered protein expression was verified by comparison to non-CVID tonsils and lymph nodes using CyTOF analysis. Tissue localization of cells was determined by multi-fluorescence imaging.Transcriptome analysis of sorted TFH cells revealed an enrichment of cytotoxicity-associated gene sets in CVIDc patients. Extended immune phenotyping identified different cytotoxic CD4 memory populations expressing T-bet, EOMES, CRTAM, perforin, and granzymes. One cluster co-expressing markers of TFH differentiation CXCR5, ICOS, and PD1 was expanded in CVIDc lymph nodes. Histological sections confirmed the increase in Granzyme-B+EOMES+ CD4 cells within GCs of patients' lymph nodes. Only few of these cells circulate in peripheral blood.Our study reports for the first time that the type 1 polarization in lymph nodes of CVIDc patients is associated with an expansion of a distinct cytotoxic CD4 TFH cell cluster within GCs which is only poorly reflected in peripheral blood. As a detrimental role of these cells has been implied in the context of autoimmunity and chronic infection further investigations are required to explore their role in the GC failure and immune dysregulation in CVID patients.
Keyword(s): CD4 T cells ; CVID ; Common variable immunodeficiency ; CyTOF ; RNAseq ; T follicular helper cell ; cytotoxicity ; lymph node ; type 1 polarization
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