Oligoclonal CD4 + CXCR5 + T cells with a cytotoxic phenotype appear in tonsils and blood.

Autor: Liang C; Functional Genomics and Systems Biology Group, Department of Bioinformatics, Biocenter, Julius-Maximilians-University Würzburg, Würzburg, Germany.; Institute of Immunology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany., Spoerl S; Department of Internal Medicine 5, Hematology/Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Xiao Y; Institute of Pathology, Julius-Maximilians-University Würzburg, Würzburg, Germany., Habenicht KM; Division of Genetics, Department Biology, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany., Haeusl SS; Institute of Pathology, Julius-Maximilians-University Würzburg, Würzburg, Germany., Sandner I; Department of Internal Medicine 5, Hematology/Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Winkler J; Department of Internal Medicine 5, Hematology/Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Strieder N; Leibniz Institute for Immunotherapy, Regensburg, Germany., Eder R; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany., Stanewsky H; Leibniz Institute for Immunotherapy, Regensburg, Germany., Alexiou C; Department of Otorhinolaryngology, Head & Neck Surgery, Else Kröner-Fresenius-Foundation-Professorship, Section of Experimental Oncology & Nanomedicine (SEON), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany., Dudziak D; Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.; Institute of Immunology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany., Rosenwald A; Institute of Pathology, Julius-Maximilians-University Würzburg, Würzburg, Germany.; Comprehensive Cancer Centre Mainfranken, Julius-Maximilians-University of Würzburg, Würzburg, Germany., Edinger M; Leibniz Institute for Immunotherapy, Regensburg, Germany.; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany., Rehli M; Leibniz Institute for Immunotherapy, Regensburg, Germany.; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany., Hoffmann P; Leibniz Institute for Immunotherapy, Regensburg, Germany.; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany., Winkler TH; Division of Genetics, Department Biology, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany., Berberich-Siebelt F; Institute of Pathology, Julius-Maximilians-University Würzburg, Würzburg, Germany. path230@mail.uni-wuerzburg.de.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Jul 18; Vol. 7 (1), pp. 879. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1038/s42003-024-06563-1
Abstrakt: In clinical situations, peripheral blood accessible CD3 + CD4 + CXCR5 + T-follicular helper (T FH ) cells may have to serve as a surrogate indicator for dysregulated germinal center responses in tissues. To determine the heterogeneity of T FH cells in peripheral blood versus tonsils, CD3 + CD4 + CD45RA - CXCR5 + cells of both origins were sorted. Transcriptomes, TCR repertoires and cell-surface protein expression were analysed by single-cell RNA sequencing, flow cytometry and immunohistochemistry. Reassuringly, all blood-circulating CD3 + CD4 + CXCR5 + T-cell subpopulations also appear in tonsils, there with some supplementary T FH characteristics, while peripheral blood-derived T FH cells display markers of proliferation and migration. Three further subsets of T FH cells, however, with bona fide T-follicular gene expression patterns, are exclusively found in tonsils. One additional, distinct and oligoclonal CD4 + CXCR5 + subpopulation presents pronounced cytotoxic properties. Those 'killer T FH (T FK ) cells' can be discovered in peripheral blood as well as among tonsillar cells but are located predominantly outside of germinal centers. They appear terminally differentiated and can be distinguished from all other T FH subsets by expression of NKG7 (TIA-1), granzymes, perforin, CCL5, CCR5, EOMES, CRTAM and CX3CR1. All in all, this study provides data for detailed CD4 + CXCR5 + T-cell assessment of clinically available blood samples and extrapolation possibilities to their tonsil counterparts.
(© 2024. The Author(s).)
Databáze: MEDLINE
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