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

ABSTRACT: 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.

SUBMITTER: Liang C 

PROVIDER: S-EPMC11258247 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature