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Cited by 355

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 access
Cannons, Jennifer L, Lau, Peggy, Ghumman, Birinder, DeBenedette, Mark A, Yagita, Hideo, Okumura, Ko, Watts, Tania H·2001·The Journal of Immunology
DOI 10.4049/jimmunol.167.3.1313
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Abstract

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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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
DOI
10.4049/jimmunol.167.3.1313
OpenAlex
W2157620455
Cited by
355
References
57
FWCI
9.03
Type
journal article
Language
en
Open access
bronze

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