B70 antigen is a second ligand for CTLA-4 and CD28

Azuma, Miyuki; Ito, Daisuke; Yagita, Hideo; Okumura, Ko; Phillips, Joseph H.; Lanier, Lewis L.; Somoza, Chamorro

doi:10.1038/366076a0

Cited by 868 publications

(477 citation statements)

References 24 publications

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“…One of the best known, a crucial costimulatory molecule, is CD28, which is expressed on most T cells and thymocytes. Ligation of CD28 by its ligands, CD80 (B7, B7-1) [7,8] or CD86 (B70, B7-2) [9,10] costimulates T cell proliferation, cytokine production and generation of cytotoxic T lymphocytes (CTL) [11,12].…”

Section: Introductionmentioning

confidence: 99%

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Kaneko

Saito

Hashimoto

et al. 1996

Clinical and Experimental Immunology

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SUMMARYCD28 on T cells provides a potent costimulatory signal for T cell activation. Down-regulation of CD28 on peripheral T cells has been reported in certain clinical conditions, but full studies on the mechanism and biological significance have not been performed. Our extensive phenotype analysis of peripheral blood lymphocytes (PBL) from SLE patients revealed that the absolute number of CD28 T cells of both CD4 and CD8 phenotypes was selectively decreased, while that of CD28 ÿ T cells was maintained. CD28 T cells from SLE patients exhibited mostly normal proliferative responses to both CD28-dependent and -independent stimulations. In contrast, CD28 ÿ T cells were hyporesponsive to anti-CD3 stimulation in both SLE and normal controls. These results implied that the selective decrease of CD28 T cells in SLE does not result from a hyporesponsiveness of CD28 T cells. To investigate the reason for the selective loss of CD28 T cells, we determined the appearance of apoptotic cells in culture with or without anti-CD3 stimulation. Apoptotic cells defined by merocyanine (MC)540 were gradually increased from 12 h to 24 h. Anti-CD3-induced apoptosis of CD28 T cells was significantly accelerated in SLE, whereas apoptosis of CD28 ÿ T cells was hardly detected in both SLE and normal controls. Comparative analysis between CD28 and CD28 ÿ T cells on CD95 (Fas) and Bcl-2 expression, which are related to activation-induced cell death (AICD), did not show a major difference, although CTLA4, which has been demonstrated to transmit an apoptosis-inducing signal, was expressed only on CD28 T cells. Our results suggest that CD28-mediated costimulation influences T cell susceptibility to AICD and may be involved in T cell lymphopenia in SLE.

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Section: Introductionmentioning

confidence: 99%

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Kaneko

Saito

Hashimoto

et al. 1996

Clinical and Experimental Immunology

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“…8 B7 -1 (CD80 ) is a member of the B7 family of co -stimulatory molecules expressed on antigen-presenting cells, and its interaction with CD28 on the T cell is required at the time of TCR engagement to mediate T-cell activation. 9 Because tumor cells generally lack CD80 and other co-stimulatory molecules, the antigen± MHC /TCR interaction of tumor and T cell, rather than lead to recognition of tumor-associated antigen, instead leads to anergy. 10,11 Consistent with this scenario, the introduction of CD80 into tumor cells can lead to tumor rejection and confers a protective, immune -based, antitumor response against subsequent challenge with unmodified parental cells.…”

mentioning

confidence: 99%

Tricistronic viral vectors co-expressing interleukin-12 (1L-12) and CD80 (B7-1) for the immunotherapy of cancer: Preclinical studies in myeloma

Wen

Mandelbaum

et al. 2001

Cancer Gene Ther

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Synergy between interleukin -12 ( IL -12 ) and B7 -1 ( CD80 ) for cancer immunotherapy has previously been demonstrated in animal models of breast cancer, lymphoma, and multiple myeloma. With a view to human clinical application, tricistronic retroviral and adenovirus vectors co -expressing IL -12 ( IL -12p40 plus IL -12p35 ) and CD80 were constructed by utilizing two internal ribosome entry site ( IRES ) sequences to link the three cDNAs. A murine stem cell virus ( MSCV ) -based retroviral vector ( MSCV -hIL12.B7 ) utilized distinct IRES sequences from the encephalomyocarditis virus ( EMCV ) and the foot -and -mouth disease virus ( FMCV ), whereas Ad5 -based adenovirus vectors contained transcriptional units with two EMCV IRES sequences under the control of murine ( AdMh12.B7 ) or human ( AdHh12.B7 ) cytomegalovirus promoters. AdMh12.B7 was found to consistently direct higher levels of IL -12 and CD80 expression than AdHh12.B7 following infection of a number of human tumor cell lines. In preclinical studies, the human myeloma cell line U266 was infected with MSCV -hIL12.B7 and a resulting clonal cell line, U / MSCV -h12.B7, was generated with stable expression of CD80 and secreting IL -12 at 1 ng / 24 h / 10 6 cells. By comparison, following AdMh12.B7 infection, 81% of infected U266 cells ( U / AdMh12.B7 ) expressed CD80 and secreted IL -12 at 25 ± 50 ng / 24 h / 10 6 cells. Both engineered myeloma cell lines stimulated enhanced allogeneic mixed lymphocyte proliferation and provoked increases in cytotoxic T -lymphocyte responses and -interferon release from normal donor lymphocytes exposed to parental U266 cells. These results suggest potential clinical utility of AdMh12.B7 in immunotherapy strategies for the treatment of multiple myeloma and other cancers.

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“…It is reported that both B7-1 and B7-2 are the ligands for CTLA4 and expressed on cell surface as membrane antigens [8][9][10][11]. CTLA4Ig binds these molecules with very high affinity [1].…”

Section: Ctla4ig From Transfected Mm1 Cells Binds Effectively To B7 Mmentioning

confidence: 99%

“…B7 molecules are expressed on a variety of cell types, including dentritic cells, B cells, T-cells and macrophages [8][9][10][11]. CTLA4Ig, a soluble form of CTLA4, could block B7 and CD28/CTLA4 pathway and results in the inhibitation of Tcell activation and autoimmune response [12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Expression of a soluble form of CTLA4 on macrophage and its biological activity

et al. 1999

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Interaction between cytotoxic T lymphocyte-asso-ciated antigen-4 (CTLA4, CD152) and B7 molecules (B7-1 and B7-2) is of importance in the cellular events of lymphocyte, including antigen-specific T-cell activation and induction of autoreactive T-cell. We describe here the first introduction of a murine soluble CTLA4 gene, CTLA4Ig, to Mm1 cells, a macrophagic cell line. CTLA4Ig was successfully expressed on Mm1 cells and the expressed CTLA4Ig was found to be functionally active in their binding to B7 molecules by flow cytometry and immunofl-uorescence studies. The biological activity of CTLA4Ig from the transfected Mm1 cells was studied and showed inhibitory activity on mixed lymphocyte culture. A high CTLA4Ig producing macrophagic cell line was obtained. As Mm1 cells were regarded as difficult for gene transfection and there had so far been no report on expression of CTLA4Ig gene on Mm1 cells, these results suggested that the CTLA4Ig ex- 190Expression of CTLA4 on Mm1 and its biological activity pressing Mm1 cells could be useful for analysis of CTLA4 and B7 molecule interaction in both macrophage and T-cell.

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B70 antigen is a second ligand for CTLA-4 and CD28

Cited by 868 publications

References 24 publications

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Tricistronic viral vectors co-expressing interleukin-12 (1L-12) and CD80 (B7-1) for the immunotherapy of cancer: Preclinical studies in myeloma

Expression of a soluble form of CTLA4 on macrophage and its biological activity

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