B7-1 Costimulatory Molecule Is Critical for the Development of Experimental Autoimmune Myasthenia Gravis

Abstract

Following immunization with acetylcholine receptor (AChR), MHC class II-restricted, AChR-specific CD4 cell activation is critical for the development of experimental autoimmune myasthenia gravis (EAMG) in C57BL/6 mice. To study the contributions of B7-1 and B7-2 costimulatory molecules in EAMG, B7-1, B7-2, and B7-1/B7-2 gene knockout (KO) mice were immunized with Torpedo AChR in CFA. Compared with wild-type C57BL6 mice, B7-1 and B7-1/2 KO mice were resistant to EAMG development. B7-1 KO mice had reduced anti-AChR Ab compared with C57BL/6 mice. However, neither B7-1 nor B7-2 gene disruption impaired AChR-induced or dominant α146–162 peptide-induced in vitro lymphoproliferative responses. Blocking of the B7-1 or B7-2 molecule by specific mAbs in vivo led to a reduction in the AChR-specific lymphocyte response, and the reduction was more pronounced in mice treated with anti-B7-2 Ab. The findings implicate B7-1 molecules as having a critical role in the induction of EAMG, and the resistance of B7-1 KO mice is associated with suppressed humoral, rather than suppressed AChR-specific, T cell responses. The data also point to B7-2 molecules as being the dominant costimulatory molecules required for AChR-induced lymphocyte proliferation.

NK cells that are activated by CXCL10 can kill dormant tumor cells that resist CTL-mediated lysis and can express B7-H1 that stimulates T cells

“…17,[20][21][22][23] In vitro treatment of mouse and human NK cells with chemokines and cytokines Purified NK cells from naive mice were incubated with recombinant IL-2 (200 IU/mL), IL-3 (200 IU/mL), IL-4 (10 ng/mL), IL-5 (30 IU/mL), IL-7 (50 ng/mL), IL-10 (100 IU/mL), IL-12 (20 IU/mL), IL-13 (50 ng/mL), IL-15 (100 ng/mL), IL-18 (50 ng/mL), GM-CSF (100 ng/mL), IFN-␥ (200 IU/mL), TNF-␣ (500 IU/mL), CXCL9 (100 ng/mL), CXCL10 (100 ng/mL), CXCL11 (200 ng/mL), CXCL12 (40 ng/mL), CCL3 (100 ng/mL), CCL5 (100 ng/mL), or CCL11 (100 ng/mL). Flow cytometry analysis of B7-H1 expression was performed after 6 and 24 hours of incubation.…”

A Novel Monoclonal Antibody against Human CD80 and its Immune Protection in a Mouse Lupus-like Disease

“…The interaction of C080 or C086 with C028 on T cells promotes T-cell proliferation, regulates Thl/Th2 differentiation, and monitors antibody production and isotype switching (2). However, it has been demonstrated that C080 and C086 may contribute to the pathogenesis of a variety of immune-mediated diseases such as autoimmune disease and transplant rejection (3)(4)(5)(6). Thus, blockage of signal C028 ligated with C080 or C086 becomes the basis of many potential therapies for autoimmune disease and transplantation.…”

B7-2 (CD86) Controls the Priming of Autoreactive CD4 T Cell Response against Pancreatic Islets

“…These observations further add to the growing body of evidence that B7-2 plays a pivotal role in the initial priming of T cells. In the experimental autoimmune myasthenia gravis model, B7-2 has been implicated in the activation of acetylcholine receptor-specific T cells (26). In addition, a blockade of B7-2 has been shown to induce CD4 T cell anergy (27) and also inhibit CD4 T cell activation (28).…”

“…Indeed, costimulation through CD28 has been shown to promote T cell survival and activation (41,42). Whereas the blockade of B7-2 induces CD4 T cell unresponsiveness (26,27), reflecting the net induction of tolerance through the TCR in the absence of costimulation has been reported to induce rapid Fasdependent, proliferation-independent death of purified naive CD4 T cells (43). It is also possible that this CD4 T cell death may be mediated through engagement of B7-1 alone or inhibitory receptors during T cell activation.…”

“…Furthermore, B7-1 has been shown to play an important role in the induction of EAE (11) and experimental autoimmune myasthenia gravis (26). Indeed, enhanced B7-1 expression has been linked to the spontaneous autoimmune peripheral polyneuropathy in B7-2KO NOD mice.…”