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• W2464400647 abstract "Abstract Detection of Ag-specific CD4+ T cells is central to the study of many human infectious diseases, vaccines, and autoimmune diseases. However, such cells are generally rare and heterogeneous in their cytokine profiles. Identification of Ag-specific germinal center (GC) T follicular helper (Tfh) cells by cytokine production has been particularly problematic. The function of a GC Tfh cell is to selectively help adjacent GC B cells via cognate interaction; thus, GC Tfh cells may be stingy cytokine producers, fundamentally different from Th1 or Th17 cells in the quantities of cytokines produced. Conventional identification of Ag-specific cells by intracellular cytokine staining relies on the ability of the CD4+ T cell to generate substantial amounts of cytokine. To address this problem, we have developed a cytokine-independent activation-induced marker (AIM) methodology to identify Ag-specific GC Tfh cells in human lymphoid tissue. Whereas Group A Streptococcus–specific GC Tfh cells produced minimal detectable cytokines by intracellular cytokine staining, the AIM method identified 85-fold more Ag-specific GC Tfh cells. Intriguingly, these GC Tfh cells consistently expressed programmed death ligand 1 upon activation. AIM also detected non-Tfh cells in lymphoid tissue. As such, we applied AIM for identification of rare Ag-specific CD4+ T cells in human peripheral blood. Dengue, tuberculosis, and pertussis vaccine–specific CD4+ T cells were readily detectable by AIM. In summary, cytokine assays missed 98% of Ag-specific human GC Tfh cells, reflecting the biology of these cells, which could instead be sensitively identified by coexpression of TCR-dependent activation markers." @default.
• W2464400647 created "2016-07-22" @default.
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• W2464400647 date "2016-08-01" @default.
• W2464400647 modified "2023-10-16" @default.
• W2464400647 title "A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood" @default.
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• W2464400647 doi "https://doi.org/10.4049/jimmunol.1600318" @default.
• W2464400647 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4955771" @default.
• W2464400647 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27342848" @default.
• W2464400647 hasPublicationYear "2016" @default.
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