The B cell surface molecule designated B7 has been shown to be expressed by activated human B cells and monocytes and to be a ligand for the CD28 and CTLA-4 molecules on T cells. B7/CD28 interactions can provide a second signal to T cells (in addition to occupancy of the T cell antigen receptor) that is needed for T cell activation. COS cells transfected with the mouse homologue of B7 have been demonstrated to provide a stimulatory signal to murine and human T cells. In this report we describe a rat anti-mouse B7 mAb designated 1G10. Scatchard and/or FACS analyses utilizing 1G10 demonstrated that B7 was not expressed on resting splenic T cells or B cells, but could be induced at high levels on B cells cocultured with a syngeneic I-Ak-restricted autoreactive T cell hybridoma. Furthermore, activation of B cells with dibutyryl-cAMP (db-cAMP), a second messenger for class II MHC signaling, or with LPS induced the expression of B7 and the two agents showed additive effects. In contrast to B cells, freshly isolated mouse peritoneal macrophages constitutively expressed B7. Antibody-blocking experiments indicated that anti-B7 antibody partially inhibited T cell proliferative responses to primary antigenic stimulation but had no effect on the responses of previously activated T cells to antigenic restimulation.
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http://dx.doi.org/10.1006/cimm.1994.1030 | DOI Listing |
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Gastrointestinal Unit, Department of Medicine, Royal Marsden Hospital, London and Surrey, UK. Electronic address:
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Institute of Marine Science and Technology, Shandong University, Qingdao, Shandong 266237, China. Electronic address:
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Wuya Faculty of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
Antidrug antibodies (ADAs) against biologics present a major challenge for sustained biotherapy, including enzyme replacement therapies and adeno-associated virus (AAV) gene therapies. These antibodies arise from undesirable immune responses, leading to altered pharmacokinetics, reduced efficacy, and adverse reactions. In this study, we introduced a rationally designed lipid-rapamycin (Rapa)-based nanovaccine to restore immune tolerance to biologics and overcome drug resistance.
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