The DOI matches its Crossref record.
Characterization of CD4+ CTLs Ex Vivo
Abstract
The cytotoxic potential of CD8+ T cells and NK cells plays a crucial role in the immune response to pathogens. Although in vitro studies have reported that CD4+ T cells are also able to mediate perforin-mediated killing, the in vivo existence and relevance of cytotoxic CD4+ T cells have been the subject of debate. Here we show that a population of CD4+ perforin+ T cells is present in the circulation at low numbers in healthy donors and is markedly expanded in donors with chronic viral infections, in particular HIV infection, at all stages of the disease, including early primary infection. Ex vivo analysis shows that these cells have cytotoxic potential mediated through the release of perforin. In comparison with more classical CD4+ T cells, this subset displays a distinct surface phenotype and functional profile most consistent with end-stage differentiated T cells and include Ag experienced CD4+ T cells. The existence of CD4+ cytotoxic T cells in vivo at relatively high levels in chronic viral infection suggests a role in the immune response.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Wilkinson, T. M., Li, C. K. F., Chui, C. S. C., Huang, A. K. Y., Perkins, M., Liebner, J. C., Lambkin-Williams, R., Gilbert, A., Oxford, J., Nicholas, B., et al. (2012) · Nature Medicine · doi:10.1038/nm.2612 · Cited by 974
Self-citationDuration of antiviral immunity after smallpox vaccination
Hammarlund, E., Lewis, M. W., Hansen, S. G., Strelow, L. I., Nelson, J. A., Sexton, G. J., Hanifin, J. M., & Slifka, M. K. (2003) · Nature Medicine · doi:10.1038/nm917 · Cited by 946
The who's who of T ‐cell differentiation: Human memory T ‐cell subsets
Mahnke, Y. D., Brodie, T. M., Sallusto, F., Roederer, M., & Lugli, E. (2013) · European Journal of Immunology · doi:10.1002/eji.201343751 · Cited by 817
Phenotype and function of human T lymphocyte subsets: Consensus and issues
Appay, V., van Lier, R. A. W., Sallusto, F., & Roederer, M. (2008) · Cytometry Part A · doi:10.1002/cyto.a.20643 · Cited by 729
Self-citationSchmid, D., Pypaert, M., & Münz, C. (2007) · Immunity · doi:10.1016/j.immuni.2006.10.018 · Cited by 577
Immune Activation and CD8+ T-Cell Differentiation towards Senescence in HIV-1 Infection
Papagno, L., Spina, C. A., Marchant, A., Salio, M., Rufer, N., Little, S., Dong, T., Chesney, G., Waters, A., Easterbrook, P., et al. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020020 · Cited by 478
Self-citationCD4 CTL, a cytotoxic subset of CD4(+) T cells, their differentiation and function
Takeuchi, A., & Saito, T. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00194 · Cited by 431
Tissue-resident memory T cells populate the human brain
Smolders, J., Heutinck, K. M., Fransen, N. L., Remmerswaal, E. B. M., Hombrink, P., ten Berge, I. J. M., van Lier, R. A. W., Huitinga, I., & Hamann, J. (2018) · Nature Communications · doi:10.1038/s41467-018-07053-9 · Cited by 406
Human immunosenescence: is it infectious?
Pawelec, G., Akbar, A., Caruso, C., Solana, R., Grubeck‐Loebenstein, B., & Wikby, A. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00271.x · Cited by 405
Mucida, D., Husain, M. M., Muroi, S., van Wijk, F., Shinnakasu, R., Naoe, Y., Reis, B. S., Huang, Y., Lambolez, F., Docherty, M., et al. (2013) · Nature Immunology · doi:10.1038/ni.2523 · Cited by 376
Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians
Hashimoto, K., Kouno, T., Ikawa, T., Hayatsu, N., Miyajima, Y., Yabukami, H., Terooatea, T., Sasaki, T., Suzuki, T., Valentine, M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907883116 · Cited by 343
Brown, D. M., Dilzer, A. M., Meents, D. L., & Swain, S. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.5.2888 · Cited by 282
Contributions of humoral and cellular immunity to vaccine-induced protection in humans
Amanna, I. J., & Slifka, M. K. (2011) · Virology · doi:10.1016/j.virol.2010.12.016 · Cited by 263
Precursors of human CD4 + cytotoxic T lymphocytes identified by single-cell transcriptome analysis
Patil, V. S., Madrigal, A., Schmiedel, B. J., Clarke, J., O’Rourke, P., de Silva, A. D., Harris, E., Peters, B., Seumois, G., Weiskopf, D., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aan8664 · Cited by 262
Śledzińska, A., Vila de Mucha, M., Bergerhoff, K., Hotblack, A., Demane, D. F., Ghorani, E., Akarca, A. U., Marzolini, M. A. V., Solomon, I., Vargas, F. A., et al. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.007 · Cited by 228
Cytomegalovirus Infection: A Driving Force in Human T Cell Immunosenescence
KOCH, S., LARBI, A., ÖZCELIK, D., SOLANA, R., GOUTTEFANGEAS, C., ATTIG, S., WIKBY, A., STRINDHALL, J., FRANCESCHI, C., & PAWELEC, G. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1396.043 · Cited by 242
Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?
Juno, J. A., van Bockel, D., Kent, S. J., Kelleher, A. D., Zaunders, J. J., & Munier, C. M. L. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00019 · Cited by 195
Self-citationThe chromatin accessibility signature of human immune aging stems from CD8+ T cells
Ucar, D., Márquez, E. J., Chung, C.-H., Marches, R., Rossi, R. J., Uyar, A., Wu, T.-C., George, J., Stitzel, M. L., Palucka, A. K., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20170416 · Cited by 200
Vescovini, R., Biasini, C., Fagnoni, F. F., Telera, A. R., Zanlari, L., Pedrazzoni, M., Bucci, L., Monti, D., Medici, M. C., Chezzi, C., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.6.4283 · Cited by 173
Premature ageing of the immune system: the cause of AIDS?
Appay, V., & Rowland-Jones, S. L. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02338-4 · Cited by 173
Self-citation(2003) · doi:10.1186/ar974 · Cited by 156
Cytokine and Chemokine Signals of T‐Cell Exclusion in Tumors
Zhang, Y., Guan, X.-Y., & Jiang, P. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.594609 · Cited by 133
Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus
Beck, O., Topp, M. S., Koehl, U., Roilides, E., Simitsopoulou, M., Hanisch, M., Sarfati, J., Latgé, J. P., Klingebiel, T., Einsele, H., et al. (2006) · Blood · doi:10.1182/blood-2005-04-1660 · Cited by 127
Zhang, B., Li, P., Wang, E., Brahmi, Z., Dunn, K. W., Blum, J. S., & Roman, A. (2003) · Virology · doi:10.1016/s0042-6822(03)00103-x · Cited by 108
Broadley, I., Pera, A., Morrow, G., Davies, K. A., & Kern, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00195 · Cited by 103
CD40L expression permits CD8+ T cells to execute immunologic helper functions
Frentsch, M., Stark, R., Matzmohr, N., Meier, S., Durlanik, S., Schulz, A. R., Stervbo, U., Jürchott, K., Gebhardt, F., Heine, G., et al. (2013) · Blood · doi:10.1182/blood-2013-02-483586 · Cited by 100
Histone deacetylases 1 and 2 restrain CD4+ cytotoxic T lymphocyte differentiation
Preglej, T., Hamminger, P., Luu, M., Bulat, T., Andersen, L., Göschl, L., Stolz, V., Rica, R., Sandner, L., Waltenberger, D., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.133393 · Cited by 36
Longevity of T-Cell Memory following Acute Viral Infection
Walker, J. M., & Slifka, M. K. (2010) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4419-6451-9_8 · Cited by 30
Metadata
- Authors
- Appay, V., Zaunders, J. J., Papagno, L., Sutton, J., Jaramillo, A., Waters, A., Easterbrook, P., Grey, P., Smith, D., McMichael, A. J., Cooper, D. A., Rowland-Jones, S. L., & Kelleher, A. D.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-06-01
- Volume
- 168
- Issue
- 11
- Pages
- 5954-5958
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2163007870
- Cited by
- 545
- References
- 0
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
