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B7-1 but not B7-2 efficiently costimulates CD8+ T lymphocytes in the P815 tumor system in vitro
Abstract
We recently have developed a method to generate primary P815-specific CTL in vitro from normal syngeneic splenocytes by employing transfection of B7-1 combined with exogenous IL-12 and IL-6. Surprisingly, when the homologous costimulator molecule B7-2 was substituted for B7-1 in this system, no specific CTL activity was obtained. Similarly, B7-1- but not B7-2-transfected P815 cells generated alloantigen-specific CTL activity from C57BL/6, accessory cell- and CD4(+)-depleted splenocytes, and costimulated proliferation of CD8+ lymphocytes in the presence of low doses of anti-CD3 mAb. In all systems, combined expression of both B7-1 and B7-2 costimulated as effectively as B7-1 alone, arguing against delivery of a dominant negative signal by B7-2. Proliferation of allogeneic, CD4(+)-depleted splenocytes in response to P815 cells, which relies on costimulation by normal accessory cells, was inhibited by anti-B7-1 but not anti-B7-2 mAbs. Finally, indirect evidence suggested a higher avidity of B7-1+ cells than B7-2+ cells for CTLA4. Thus, at least in the context of primary stimulation by irradiated P815 transfectants, B7-1 appears to be superior to B7-2 at costimulation of CD8+ T lymphocytes.
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“Animal model studies have shown that introduction of B7-1 into tumors by transfection or blockade of inhibitory B7 family members can reduce tumor growth or result in spontaneous tumor rejection in vivo [7–13].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [12]
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Self-citation
Metadata
- Authors
- Gajewski, T. F.
- Affiliations
- Ludwig Cancer Research (BE)
- Corresponding author
- Gajewski, T F
- ORCID
- Gajewski, T F
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1996-01
- Volume
- 156
- Issue
- 2
- Pages
- 465-472
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1946324007
- Cited by
- 114
- References
- 0
- Citations by year
- 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2013: 1 · 2012: 2
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- CD80, CD86, costimulation, CD8+ T cells, cytotoxic T lymphocytes, P815 tumor cells, CTLA-4, IL-12, interleukin-6, T cell proliferation, accessory cells
- MeSH terms
- Abatacept, Animals, Antibodies, Monoclonal, Antigens, Differentiation, Base Sequence, Cells, Cultured, Cytotoxicity, Immunologic, Female, Interleukin-2, Leukemia L1210, Lymphocyte Culture Test, Mixed, Lymphocyte Activation, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Inbred DBA, Molecular Sequence Data, Recombinant Proteins, Mast-Cell Sarcoma, Specific Pathogen-Free Organisms, Spleen, T-Lymphocytes, Cytotoxic, Transfection, Tumor Cells, Cultured, Signal Transduction, CD4-Positive T-Lymphocytes, Antigens, CD, Interleukin-6, Muromonab-CD3, B7-1 Antigen, Interleukin-12, Immunoconjugates, Mice, B7-2 Antigen, CTLA-4 Antigen
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