The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
4-1BB Ligand Induces Cell Division, Sustains Survival, and Enhances Effector Function of CD4 and CD8 T Cells with Similar Efficacy
Open accessAbstract
A costimulatory member of the TNFR family, 4-1BB, is expressed on activated T cells. Although some reports have suggested that 4-1BB is primarily involved in CD8 T cell activation, in this report we demonstrate that both CD4 and CD8 T cells respond to 4-1BB ligand (4-1BBL) with similar efficacy. CD4 and CD8 TCR transgenic T cells up-regulate 4-1BB, OX40, and CD27 and respond to 4-1BBL-mediated costimulation during a primary response to peptide Ag. 4-1BBL enhanced proliferation, cytokine production, and CTL effector function of TCR transgenic T cells. To compare CD4 vs CD8 responses to 4-1BBL under similar conditions of antigenic stimulation, we performed MLRs with purified CD4 or CD8 responders from CD28+/+ and CD28−/− mice. We found that CD8 T cells produced IL-2 and IFN-γ in a 4-1BBL-dependent manner, whereas under the same conditions the CD4 T cells produced IL-2 and IL-4. 4-1BBL promoted survival of CD4 and CD8 T cells, particularly at late stages of the MLR. CD4 and CD8 T cells both responded to anti-CD3 plus s4-1BBL with a similar cytokine profile as observed in the MLR. CD4 and CD8 T cells exhibited enhanced proliferation and earlier cell division when stimulated with anti-CD3 plus anti-CD28 compared with anti-CD3 plus 4-1BBL, and both subsets responded comparably to anti-CD3 plus 4-1BBL. These data support the idea that CD28 plays a primary role in initial T cell expansion, whereas 4-1BB/4-1BBL sustains both CD4 and CD8 T cell responses, as well as enhances cell division and T cell effector function.
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Cites
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Cited by
Zhong, X.-S., Matsushita, M., Plotkin, J., Riviere, I., & Sadelain, M. (2010) · Molecular Therapy · doi:10.1038/mt.2009.210 · Cited by 543
Wolfl, M., Kuball, J., Ho, W. Y., Nguyen, H., Manley, T. J., Bleakley, M., & Greenberg, P. D. (2007) · Blood · doi:10.1182/blood-2006-11-056168 · Cited by 458
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Choi, W., Lee, Y., Choi, B. K., Park, B.-M., Kim, Y. H., Yun, T., Lee, W. J., Yoo, H., Baek, J. Y., Woo, S. M., et al. (2023) · Cytotherapy · doi:10.1016/j.jcyt.2023.07.006 · Cited by 6
Metadata
- Authors
- Cannons, J. L., Lau, P., Ghumman, B., DeBenedette, M. A., Yagita, H., Okumura, K., & Watts, T. H.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-08-01
- Volume
- 167
- Issue
- 3
- Pages
- 1313-1324
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2157620455
- Cited by
- 355
- References
- 57
- FWCI
- 9.03
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Cannons, J. L., Lau, P., Ghumman, B., DeBenedette, M. A., Yagita, H., Okumura, K., & Watts, T. H. (2001). 4-1BB Ligand Induces Cell Division, Sustains Survival, and Enhances Effector Function of CD4 and CD8 T Cells with Similar Efficacy. The Journal of Immunology. https://doi.org/10.4049/jimmunol.167.3.1313
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