The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Gr-1+ Myeloid Cells Derived from Tumor-Bearing Mice Inhibit Primary T Cell Activation Induced Through CD3/CD28 Costimulation
Abstract
Activation of T cells is a necessary step in the development of a specific antitumor immune response. In the present study, we evaluated the ability of Gr-1+ myeloid cells, derived from the bone marrow or spleen of tumor-bearing mice, to inhibit CD3/CD28-mediated T cell activation. Using flow cytometry, we found that growth of a murine colon carcinoma (MCA-26) induces a significant increase in the number of Gr-1+ and Gr-1+/Mac-1+ myeloid cells in both bone marrow and spleen of the tumor host. The proliferative response of T cells was dramatically decreased when naive T cells were activated by anti-CD3 and anti-CD28 Abs in the presence of a myeloid-enriched cell fraction derived from spleen or bone marrow of tumor-bearing mice vs the bone marrow of naive mice. Reversal of the inhibitory effect could be achieved by adding a combination of MnTBAP (manganese [III] tetrakis [4-benzoic acid]) porphyrin and l-NMMA (NG-monomethyl-l-arginine), a superoxide dismutase mimetic and inducible NO synthase inhibitor, respectively, or by depletion of the Gr-1-positive cells. IFN-γ, which is endogenously produced by CD3/CD28-stimulated naive T cells, is involved in induction of the inhibitory activity of myeloid cells. Importantly, when T cells pre-activated with anti-CD3 Abs were used as responder cells, the bone marrow- or spleen-derived Gr-1+ myeloid cells were unable to suppress CD3/CD28-induced T cell proliferation. Our findings suggest that one mechanism by which an increased number of immune suppressive Gr-1+ cells can induce T cell unresponsiveness or immune tolerance in tumor hosts could be through peroxynitrite production upon primary T cell activation.
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Cites
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Cited by
Myeloid-derived-suppressor cells as regulators of the immune system
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Immunosuppressive networks in the tumour environment and their therapeutic relevance
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Regulation of immune responses by L-arginine metabolism
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Inhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608
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Self-citation
Metadata
- Authors
- Kusmartsev, S. A., Li, Y., & Chen, S.-H.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-07
- Volume
- 165
- Issue
- 2
- Pages
- 779-785
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2168200596
- Cited by
- 355
- References
- 30
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- closed
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- Kusmartsev, S. A., Li, Y., & Chen, S.-H. (2000). Gr-1+ Myeloid Cells Derived from Tumor-Bearing Mice Inhibit Primary T Cell Activation Induced Through CD3/CD28 Costimulation. The Journal of Immunology. https://doi.org/10.4049/jimmunol.165.2.779
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