The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Trans-Endocytosis of CD80 and CD86: A Molecular Basis for the Cell-Extrinsic Function of CTLA-4
Open accessAbstract
Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“CTLA-4 may also remove CD80 and CD86 (including their cytoplasmic domains) from the cell surfaces of antigen-presenting cells via trans-endocytosis (24), therefore reducing the availability of these stimulatory receptors to other CD28-expressing T cells.”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [24]
In the citing paper
“It is thought that the blockade of CTLA-4 most likely impacts the stage of T cell activation in the draining lymph nodes when CTLA-4 expressing Tregs remove CD80/CD86 from the surface of antigen-presenting cells, thereby reducing their ability to effectively stimulate tumor-specific T cells (24).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [24]
In the citing paper
“Additionally, CTLA-4 could capture, remove, and degrade its ligands CD80/CD86 from nearby APCs by trans-endocytosis, further hampering the co-stimulatory signal [125].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [125]
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
Cites
CTLA-4 Control over Foxp3 + Regulatory T Cell Function
Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., & Sakaguchi, S. (2008) · Science · doi:10.1126/science.1160062 · Cited by 2,956
Tivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90125-6 · Cited by 2,914
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., & Mak, T. W. (1995) · Science · doi:10.1126/science.270.5238.985 · Cited by 2,766
Read, S., Malmström, V., & Powrie, F. M. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.2.295 · Cited by 2,206
Plat-E: an efficient and stable system for transient packaging of retroviruses
MORITA, S., Kojima, T., & Kitamura, T. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301206 · Cited by 1,660
Peggs, K. S., Quezada, S. A., Chambers, C. A., Korman, A. J., & Allison, J. P. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20082492 · Cited by 967
CD28 and CTLA-4 coreceptor expression and signal transduction
Rudd, C. E., Taylor, A., & Schneider, H. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00770.x · Cited by 898
Onishi, Y., Fehervari, Z. T., Yamaguchi, T., & Sakaguchi, S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711106105 · Cited by 754
B cells acquire antigen from target cells after synapse formation
Batista, F. D., Iber, D., & Neuberger, M. S. (2001) · Nature · doi:10.1038/35078099 · Cited by 629
A MOLECULAR PERSPECTIVE OF CTLA-4 FUNCTION
Teft, W. A., Kirchhof, M. G., & Madrenas, J. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090535 · Cited by 526
Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo
Read, S., Greenwald, R., Izcue, A., Robinson, N., Mandelbrot, D., Francisco, L., Sharpe, A. H., & Powrie, F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.7.4376 · Cited by 434
Hikosaka, Y., Nitta, T., Ohigashi, I., Yano, K., Ishimaru, N., Hayashi, Y., Matsumoto, M., Matsuo, K., Penninger, J. M., Takayanagi, H., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.06.018 · Cited by 433 · cited 1×
“Retrovirus infection of cells was performed as described previously (33).”
BackgroundChambers, C. A., Sullivan, T. J., & Allison, J. P. (1997) · Immunity · doi:10.1016/s1074-7613(00)80406-9 · Cited by 406
Oderup, C., Cederbom, L., Makowska, A. M., Cilio, C., & Ivars, F. (2006) · Immunology · doi:10.1111/j.1365-2567.2006.02362.x · Cited by 335
Rac-dependent trans-endocytosis of ephrinBs regulates Eph–ephrin contact repulsion
Marston, D. J., Dickinson, S., & Nobes, C. D. (2003) · Nature Cell Biology · doi:10.1038/ncb1044 · Cited by 301
CD40 Ligation Releases Immature Dendritic Cells from the Control of Regulatory CD4+CD25+ T Cells
Serra, P., Amrani, A., Yamanouchi, J., Han, B., Thiessen, S., Utsugi, T., Verdaguer, J., & Santamaría, P. (2003) · Immunity · doi:10.1016/s1074-7613(03)00327-3 · Cited by 291
Davis, D. M. (2007) · Nature reviews. Immunology · doi:10.1038/nri2020 · Cited by 286
CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance
Friedline, R. H., Brown, D. S., Nguyen, H., Kornfeld, H., Lee, J., Zhang, Y., Appleby, M. W., Der, S. D., Kang, J., & Chambers, C. A. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20081811 · Cited by 266
Cutting Edge: Lymphoproliferative Disease in the Absence of CTLA-4 Is Not T Cell Autonomous
Bachmann, M. F., Köhler, G., Ecabert, B., Mak, T. W., & Köpf, M. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.3.1128 · Cited by 232
Chuang, E., Alegre, M., Duckett, C. S., Noel, P. J., Heiden, M. G. V., & Thompson, C. B. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.1.144 · Cited by 225
Iida, T., Ohno, H., Nakaseko, C., Sakuma, M., Takeda‐Ezaki, M., Arase, H., Kominami, E., Fujisawa, T., & Saito, T. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.9.5062 · Cited by 173
The bride of sevenless and sevenless interaction: Internalization of a transmembrane ligand
Cagan, R. L., Krämer, H., Hart, A. C., & Zipursky, S. L. (1992) · Cell · doi:10.1016/0092-8674(92)90442-f · Cited by 171
Schmidt, E. M., Wang, C. J., Ryan, G. A., Clough, L. E., Qureshi, O., Goodall, M. D., Abbas, A. K., Sharpe, A. H., Sansom, D. M., & Walker, L. S. K. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.1.274 · Cited by 155
Choi, J.-M., Ahn, M.-H., Chae, W.-J., Jung, Y.-G., Park, J.-C., Song, H.-M., Kim, Y.-E., Shin, J.-A., Park, C.-S., Park, J.-W., et al. (2006) · Nature Medicine · doi:10.1038/nm1385 · Cited by 138
Hudrisier, D., Aucher, A., Puaux, A., Bordier, C., & Joly, E. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.6.3637 · Cited by 102
Aucher, A., Magdeleine, E., Joly, E., & Hudrisier, D. (2008) · Blood · doi:10.1182/blood-2008-01-134155 · Cited by 97
Mead, K. I., Zheng, Y., Manzotti, C. N., Perry, L., Liu, M. K. P., Burke, F., Powner, D., Wakelam, M. J. O., & Sansom, D. M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.4803 · Cited by 89
Zheng, Y., Manzotti, C. N., Burke, F., Dussably, L., Qureshi, O., Walker, L. S. K., & Sansom, D. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.3.1683 · Cited by 88
Lack of Intrinsic CTLA-4 Expression Has Minimal Effect on Regulation of Antiviral T-Cell Immunity
Homann, D., Dummer, W., Wolfe, T., Rodrigo, E., Theofilopoulos, A. N., Oldstone, M. B. A., & von Herrath, M. G. (2005) · Journal of Virology · doi:10.1128/jvi.80.1.270-280.2006 · Cited by 56
Membranous Structures Transfer Cell Surface Proteins Across NK Cell Immune Synapses
Williams, G. S., Collinson, L., Brzostek, J., Eissmann, P., Almeida, C. R., McCann, F. E., Burshtyn, D. N., & Davis, D. M. (2007) · Traffic · doi:10.1111/j.1600-0854.2007.00603.x · Cited by 52
Preferential Transfer of Certain Plasma Membrane Proteins onto T and B Cells by Trogocytosis
Daubeuf, S., Aucher, A., Bordier, C., Salles, A., Serre, L., Gaibelet, G., Faye, J., Favre, G., Joly, E., & Hudrisier, D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008716 · Cited by 47
Trans-endocytosis of CD47 and SHPS-1 and its role in regulation of the CD47–SHPS-1 system
Kusakari, S., Ohnishi, H., Jin, F.-J., Kaneko, Y., Murata, T., Murata, Y., Okazawa, H., & Matozaki, T. (2008) · Journal of Cell Science · doi:10.1242/jcs.025015 · Cited by 34
TcR‐induced regulated secretion leads to surface expression of CTLA‐4 in CD4+CD25+ T cells
Catálfamo, M., Tai, X., Karpova, T., McNally, J. G., & Henkart, P. A. (2008) · Immunology · doi:10.1111/j.1365-2567.2008.02822.x · Cited by 21
Flagged first, then by citations
Cited by
Sorted by citations
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Oncology meets immunology: the cancer-immunity cycle.
Chen, D. S., & Mellman, I. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.012 · Cited by 6,929
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229
A guide to cancer immunotherapy: from T cell basic science to clinical practice
Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0306-5 · Cited by 4,154
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
Wei, S. C., Duffy, C. R., & Allison, J. P. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0367 · Cited by 3,088
Metadata
- Authors
- Qureshi, O. S., Zheng, Y., Nakamura, K., Attridge, K., Manzotti, C., Schmidt, E. M., Baker, J., Jeffery, L. E., Kaur, S., Briggs, Z., Hou, T. Z., Futter, C. E., Anderson, G., Walker, L. S. K., & Sansom, D. M.
- Affiliations
- University of Birmingham (GB)
- University College London (GB)
- Corresponding author
- Sansom, David M.
- ORCID
- Venue
- Science
- Published
- 2011-04-29
- Volume
- 332
- Issue
- 6029
- Pages
- 600-603
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3198051
- OpenAlex
- W2087482409
- Cited by
- 1,860
- References
- 33
- Citations by year
- 2026: 128 · 2025: 140 · 2024: 153 · 2023: 155 · 2022: 160 · 2021: 151 · 2020: 149 · 2019: 119 · 2018: 126 · 2017: 103 · 2016: 105 · 2015: 100 · 2014: 84 · 2013: 82 · 2012: 68
- FWCI
- 38.16
- Type
- journal article
- Language
- en
- Open access
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Aston Publications Explorer (Aston University) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Wellcome Trust
- Versus Arthritis (17851)
- Biotechnology and Biological Sciences Research Council (BB/H013598/1, BB/D011000/1)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CTLA-4, CD80, CD86, CD28, trans-endocytosis, costimulation, T cell regulation, T cell receptor engagement, antigen-presenting cells, ligand degradation
- MeSH terms
- Animals, Cricetulus, Dendritic Cells, Endocytosis, Cricetinae, Humans, Ligands, Lymphocyte Activation, Mice, Transgenic, Models, Biological, Ovalbumin, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, Antigens, CD, T-Lymphocyte Subsets, CHO Cells, CD28 Antigens, B7-1 Antigen, Jurkat Cells, T-Lymphocytes, Regulatory, Mice, B7-2 Antigen, CTLA-4 Antigen
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
