The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Regulation of Cell Surface Expression of CTLA-4 by Secretion of CTLA-4-Containing Lysosomes Upon Activation of CD4+ T Cells
Open accessAbstract
CTLA-4 is expressed on the surface of activated T cells and negatively regulates T cell activation. Because a low-level expression of CTLA-4 on the cell surface is sufficient to induce negative signals in T cells, the surface expression of CTLA-4 is strictly regulated. We previously demonstrated that the association of CTLA-4 with the clathrin-associated adaptor complex AP-2 induces internalization of CTLA-4 and keeps the surface expression low. However, the mechanism to induce high expression on the cell surface upon stimulation has not yet been clarified. To address this, we investigated the intracellular dynamics of CTLA-4 by analyzing its localization and trafficking in wild-type and mutant CTLA-4-transfected Th1 clones. CTLA-4 is accumulated in intracellular granules, which we identified as lysosomes. CTLA-4 is degraded in lysosomes in a short period, and the degradation process may serve as one of the mechanisms to regulate CTLA-4 expression. Upon TCR stimulation, CTLA-4-containing lysosomes are secreted as proven by the secretion of cathepsin D and β-hexosaminidase in parallel with the increase of surface expression of CTLA-4 and lysosomal glycoprotein 85, a lysosomal marker. These results suggest that the cell surface expression of CTLA-4 is up-regulated upon stimulation by utilizing a mechanism of secretory lysosomes in CD4+T cells.
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Cites
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
Krummel, M. F., & Allison, J. P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.2.459 · Cited by 2,245 · cited 1×
“First, CD28 transduces an activation signal for T cell proliferation and cytokine secretion (4–8), whereas CTLA-4 down-regulates T cell activation (9, 10).”
BackgroundSchwartz, R. H. (1992) · Cell · doi:10.1016/s0092-8674(05)80055-8 · Cited by 1,293
CD80 (B7-1) Binds Both CD28 and CTLA-4 with a Low Affinity and Very Fast Kinetics
van der Merwe, P. A., Bodian, D. L., Daenke, S., Linsley, P., & Davis, S. J. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.3.393 · Cited by 551
Cited by
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4
Qureshi, O. S., Zheng, Y., Nakamura, K., Attridge, K., Manzotti, C., Schmidt, E. M., Baker, J., Jeffery, L. E., Kaur, S., Briggs, Z., et al. (2011) · Science · doi:10.1126/science.1202947 · Cited by 1,860
CTLA-4: new insights into its biological function and use in tumor immunotherapy
Egen, J. G., Kuhns, M. S., & Allison, J. P. (2002) · Nature Immunology · doi:10.1038/ni0702-611 · Cited by 940
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
The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses
Walker, L. S. K., & Sansom, D. M. (2011) · Nature Reviews Immunology · doi:10.1038/nri3108 · Cited by 786
A snapshot of the PD-1/PD-L1 pathway
Ghosh, C., Luong, G., & Sun, Y. (2021) · Journal of Cancer · doi:10.7150/jca.57334 · Cited by 292
Metadata
- Authors
- Iida, T., Ohno, H., Nakaseko, C., Sakuma, M., Takeda-Ezaki, M., Arase, H., Kominami, E., Fujisawa, T., & Saito, T.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-11-01
- Volume
- 165
- Issue
- 9
- Pages
- 5062-5068
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2125938085
- Cited by
- 173
- References
- 3
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Iida, T., Ohno, H., Nakaseko, C., Sakuma, M., Takeda-Ezaki, M., Arase, H., Kominami, E., Fujisawa, T., & Saito, T. (2000). Regulation of Cell Surface Expression of CTLA-4 by Secretion of CTLA-4-Containing Lysosomes Upon Activation of CD4+ T Cells. The Journal of Immunology. https://doi.org/10.4049/jimmunol.165.9.5062
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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.
