The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood
Open accessAbstract
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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Cites
Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer
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Follicular Helper CD4 T Cells (T FH )
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Self-citationThe Transcriptional Repressor Bcl-6 Directs T Follicular Helper Cell Lineage Commitment
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CD4+ follicular helper T cell infiltration predicts breast cancer survival
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Cited by
Grifoni, A., Weiskopf, D., Ramirez, S. I., Mateus, J., Dan, J. M., Moderbacher, C. R., Rawlings, S. A., Sutherland, A., Premkumar, L., Jadi, R. S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.015 · Cited by 3,595
Self-citationT follicular helper cell biology: a decade of discovery and diseases
Crotty, S. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.011 · Cited by 1,591
Self-citationSelective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans
Mateus, J., Grifoni, A., Tarke, A., Sidney, J., Ramirez, S. I., Dan, J. M., Burger, Z. C., Rawlings, S. A., Smith, D. M., Phillips, E., et al. (2020) · Science · doi:10.1126/science.abd3871 · Cited by 1,120
Self-citationTarke, A., Sidney, J., Kidd, C. K., Dan, J. M., Ramirez, S. I., Yu, E. D., Mateus, J., da Silva Antunes, R., Moore, E., Rubiro, P., et al. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100204 · Cited by 540
Self-citationGuidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531
Metadata
- Authors
- Dan, J. M., Lindestam Arlehamn, C. S., Weiskopf, D., da Silva Antunes, R., Havenar-Daughton, C., Reiss, S. M., Brigger, M., Bothwell, M., Sette, A., & Crotty, S.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-01
- Volume
- 197
- Issue
- 3
- Pages
- 983-993
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2464400647
- Cited by
- 264
- References
- 66
- FWCI
- 9.09
- Type
- journal article
- Language
- en
- Open access
- green
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- Dan, J. M., Lindestam Arlehamn, C. S., Weiskopf, D., da Silva Antunes, R., Havenar-Daughton, C., Reiss, S. M., Brigger, M., Bothwell, M., Sette, A., & Crotty, S. (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. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1600318
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