ArticleJournal of immunology (Baltimore, Md. : 1950)2016
A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers.
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Who cites it
204 citing papers in PubMed.
- Children and Adults With Mild COVID-19: Dynamics of the Memory T Cell Response up to 10 Months.Frontiers in immunology · 2022Trial
- Protein/AS01Cell reports. Medicine · 2021Trial
- Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells.The Journal of experimental medicine · 2020Trial
- Subdominance and poor intrinsic immunogenicity limit humoral immunity targeting influenza HA stem.The Journal of clinical investigation · 2019Trial
- Trial
- T cell immunomonitoring: a comparative analysis of traditional and novel methods to quantify and characterize human antigen-specific T cells.Nature protocols · 2026Review
- Lung Resident T Cells Across the Spectrum of TB Infection and Disease.bioRxiv : the preprint server for biology · 2026Article
- Reproducible detection of antigen-specific T cells and Tregs via standardized and automated activation-induced marker assay workflows.Cell reports methods · 2026Article
- Pre-existing antibodies predict protection while mucosal inflammation correlates with symptomaticmedRxiv : the preprint server for health sciences · 2026Article
- Circulating T-follicular helper and type I regulatory T cells have overlapping phenotypes inbioRxiv : the preprint server for biology · 2026Article
- Characterization of a transmembrane-activating STING agonist using genetically humanized mice.Cell reports · 2026Article
- Adenosine deaminase co-immunization reverses age-associated immunosenescence by restoring germinal center T follicular helper cell function.bioRxiv : the preprint server for biology · 2026Article
- Discordant Outcomes of SARS-CoV-2 Exposure in Household Contacts.Clinical immunology communications · 2026Article
- Prediction of SARS-CoV-2 exposure through T cell activation profiles.Scientific reports · 2026Article
- Rare variable M. tuberculosis antigens induce predominant Th17 responses in human infection.JCI insight · 2026Article
- Antigen-specific TScience advances · 2026Article
- Symptomatic SARS-CoV-2 breakthrough infections broaden the repertoire of Spike-reactive CD4 T cells.mBio · 2026Article
- Dynamics of Circulating Follicular Helper and Regulatory T-Cell Memory Induced by mRNA, Inactivated, and Live-Attenuated Vaccines.Journal of immunology research · 2026Article
- Combining Activation-Induced Markers With PD-L1 Selectively Enhances Detection of Antigen-Specific T Cells in Virus-Infected Individuals.Journal of immunology research · 2026Article
- Advanced Identification of Trypanosoma cruzi-Specific CD4Methods in molecular biology (Clifton, N.J.) · 2026Article
144 more citing papers are in PubMed but not listed here.
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10 authors.
Funding
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.
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