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@ARTICLE{Friedmann:306660,
      author       = {D. Friedmann and K. J. Payne and V. Cousin and G. Andrieux
                      and K. Meng and A. E. Schlaak and S. Unger and A. Klocperk
                      and C. Geier and K. Gräwe and J. Pfeiffer and T. F. Jakob
                      and O. Hausmann and P. Anhut and M. Shabani and K. Kurowski
                      and M. Rogg and K. Aumann and M. Seidl and J. Provaznik and
                      V. Benes and M. Boerries$^*$ and T. Boettler and C. Schell
                      and S. Goldacker and B. Keller and B. Bengsch$^*$ and K.
                      Warnatz},
      title        = {{E}xpansion of a distinct cytotoxic {CD}4 {TFH}-cell
                      cluster in lymph nodes of patients with complicated {C}ommon
                      {V}ariable {I}mmunodeficiency.},
      journal      = {The journal of allergy and clinical immunology},
      volume       = {nn},
      issn         = {0091-6749},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-02653},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      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.},
      keywords     = {CD4 T cells (Other) / CVID (Other) / Common variable
                      immunodeficiency (Other) / CyTOF (Other) / RNAseq (Other) /
                      T follicular helper cell (Other) / cytotoxicity (Other) /
                      lymph node (Other) / type 1 polarization (Other)},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41314478},
      doi          = {10.1016/j.jaci.2025.09.032},
      url          = {https://inrepo02.dkfz.de/record/306660},
}