B7 Molecules

2011 ◽  
pp. 331-332
Keyword(s):  
B7 Molecules

scholarly journals B7 Costimulation Is Critical for Antibody Class Switching and CD8+ Cytotoxic T-Lymphocyte Generation in the Host Response to Vesicular Stomatitis Virus

2000 ◽  
Vol 74 (1) ◽  
pp. 203-208 ◽  
Author(s):  
Alexander J. McAdam ◽  
Evan A. Farkash ◽  
Benjamin E. Gewurz ◽  
Arlene H. Sharpe
Keyword(s):  
Viral Infection ◽  
Vesicular Stomatitis Virus ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Specific Class ◽  
Wild Type ◽  
B7 Molecules ◽  
Vesicular Stomatitis ◽  
Ctl Responses

ABSTRACT Antibody and cytotoxic T-lymphocyte (CTL) responses have critical roles in eliminating many viral infections. In addition to stimulation of the T-cell receptor, T cells require costimulatory signals to respond optimally. We evaluated the role of B7 costimulatory molecules (B7-1 and B7-2) in the immune response to viral infection using vesicular stomatitis virus (VSV) and mice lacking either B7-1 or B7-2 or both molecules. Mice lacking both B7-1 and B7-2 had essentially no anti-VSV immunoglobulin G1 (IgG1) response, decreased IgG2a responses, and normal IgM responses, while mice lacking either B7-1 or B7-2 had unaltered anti-VSV antibody responses compared to wild-type mice. Depletion of CD4+ cells further reduced the IgG2a response in mice lacking both B7 molecules, suggesting that CD4−cells may supply help for IgG2a in the absence of B7 costimulation. The absence of both B7 molecules profoundly reduced generation of both primary and secondary VSV-specific class I major histocompatibility complex (MHC)-restricted CTL, whereas VSV-specific CTL responses in mice lacking either B7-1 or B7-2 were similar to those of wild-type animals. Class I MHC-restricted CTL in wild-type mice were not dependent on CD4+ cells, suggesting that the failure of CTL in the absence of B7s is due to a lack of B7 costimulation directly to the CD8+ CTL. These data demonstrate that B7-1 and B7-2 have critical, overlapping functions in the antibody and CTL responses to this viral infection.

New forms of dog CD80 and CD86 transcripts that encode secreted B7 molecules

1999 ◽  
Vol 50 (5-6) ◽  
pp. 349-353 ◽  
Author(s):  
S. Yang ◽  
G. K. Sim
Keyword(s):  
B7 Molecules

scholarly journals Compensation for Decreased Expression of B7 Molecules on Leishmania infantum-Infected Canine Macrophages Results in Restoration of Parasite-Specific T-Cell Proliferation and Gamma Interferon Production

1999 ◽  
Vol 67 (1) ◽  
pp. 237-243 ◽  
Author(s):  
Elena Pinelli ◽  
Victor P. M. G. Rutten ◽  
Martijn Bruysters ◽  
Peter F. Moore ◽  
E. Joost Ruitenberg
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Leishmania Infantum ◽  
Cell Activation ◽  
Gamma Interferon ◽  
T Cell Proliferation ◽  
B7 Molecules ◽  
Ifn Γ

ABSTRACT Infection of humans and dogs by Leishmania infantum may result in visceral leishmaniasis, which is characterized by impaired T-cell-mediated immune responses to parasite antigens. Dogs are natural hosts of Leishmania parasites and play an important role in the transmission of the parasites to humans. In an effort to characterize the immune response in dogs infected with this intracellular pathogen, we examined how infection with L. infantum affects canine macrophages and the consequences for T-cell activation in vitro. We showed that the proliferation of T-cell lines to cognate antigen decreases to background levels when infected autologous monocyte-derived macrophages are used as antigen-presenting cells (APC). The observed reduction of antigen-specific T-cell proliferation was shown to be dependent on the parasite load and to require cell-to-cell interaction of T cells with the infected APC. In addition, we observed a decreased expression of costimulatory B7 molecules on infected monocyte-derived macrophages. The expression of other surface molecules involved in T-cell activation, such as major histocompatibility complex class I and class II, on these cells did not change upon infection, whereas the expression of intracellular adhesion molecule 1 was marginally increased. Compensation for the decreased expression of B7 molecules by the addition of B7-transfected cells resulted in the restoration of cell proliferation and gamma interferon (IFN-γ) production by a Leishmania-specific T-cell line. These results showed that for the activation of parasite-specific canine T cells producing IFN-γ, which are most likely involved in protective immunity, sufficient expression of B7 molecules on infected macrophages is required. Provision of costimulatory molecules may be an approach for immunotherapy of leishmaniaisis as well as for vaccine development.

scholarly journals The Functional Role of B7 Molecules on the Induction of Thymocyte Activation and Apoptosis

1998 ◽  
Vol 42 (8) ◽  
pp. 555-565 ◽  
Author(s):  
Naoko Aoki ◽  
Manabu Inobe ◽  
Masaaki Murakami ◽  
Ryo Abe ◽  
Hajime Lizuka
Keyword(s):  
Functional Role ◽  
B7 Molecules

Mantle Cell Lymphoma Cells Express B7 Family Molecules and B7-H1 Expression Are up-Regulated After LPS Exposure Via MEK-Dependent and PI3K/Akt-Dependent Pathways In Mantle Cell Lymphoma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3114-3114
Author(s):  
Lijuan Wang ◽  
Hanying Bao ◽  
Yang Yang ◽  
Yi Zhao ◽  
Donghua He ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mantle Cell Lymphoma ◽  
P38 Mapk ◽  
Cell Lymphoma ◽  
Akt Pathway ◽  
Lymphoma Cells ◽  
B7 Molecules ◽  
Mantle Cell ◽  
B7 Family ◽  
Specific Inhibitors

Abstract Abstract 3114 Mantle cell lymphoma (MCL) is a distinct subtype of B-cell non-Hodgkin lymphomas characterized by a specific t(11;14) (q13;q32) translocation, causing over-expression of cyclin D1. Recent studies demonstrated that B7 family molecules were not only expressed on antigen presenting cells but also on various hematopoietic malignancies, solid tumors and infiltrating immune cells and may play important roles in tumor immunology. Many cytokines could upregulate the expression of B7 molecules, however, the molecular mechanism of regulating expressions of B7 molecules is still unknown. In this study, we analyzed B7 family molecule expression on cultured mantle cell lymphoma cells and primary MCL cells by RT-PCR. We confirmed that B7 family molecules were detected in mantle cell lymphoma cell lines SP53, Jeko-1 and Mino and primary MCL cells. We next used LPS to activate TLR4 signaling pathway. Although B7 family molecules were detected in mantle cell lymphoma cells, only B7-H1 expression was greatly enhanced after LPS exposure. B7-H1 mRNA was constitutively expressed on MCL cells and was further up-regulated after LPS stimulation in dose and time dependent manners. Western blot also indicated that total and surface B7-H1 protein expression were up-regulated after stimulated by LPS. Flow cytometry demonstrated that surface B7-H1 protein expression were up-regulated after stimulated by LPS. When we knockdown TLR4, LPS stimulation did not up-regulate B7-H1 expression. To clarify the signaling pathways of LPS induced B7-H1 up-regulation in MCL cells, we incubated the SP53 and Jeko-1 cells with LPS after pretreatment with different signal transduction pathway inhibitors for 1h and detect the activity of each inhibitor. Pretreatment and coincubation of SP53 and Jeko-1 cells with the MEK1/2 inhibitor UO126 and PI3K/Akt inhibitor LY294002 strongly reduced LPS induced B7-H1 expression, indicating that the MEK1/2 and PI3K/Akt pathway are crucial for B7-H1 expression in MCL cells. We also tested whether JNK or p38, respectively, are involved in controlling the expression of B7-H1 in MCL cells. Blocking of JNK and p38 MAPK with specific inhibitors reduced B7-H1 mRNA expression, but B7-H1 protein expression was not obvious, which may be regulated after transcriptional factors. To confirm that LPS induced B7-H1 expression through a MEK and PI3K/Akt pathway pathways in MCL cells, we stimulated SP53 and Jeko-1 with LPS and analyzed the phosphorylation of ERK1/2, p38, and JNK at different time. ERK1/2, p38, and JNK phosphorylation were significantly up-regulated following LPS treatment. We confirmed that pretreatment of the cells with these specific inhibitors inhibited LPS-induced phosphorylation of ERK1/2, p38 MAPK, and JNK, respectively. In conclusion, our study demonstrated that mantle cell lymphoma cells express B7 family molecules. B7-H1 expression were up-regulated after LPS exposure via MEK-dependent and PI3K/Akt-dependent in mantle cell lymphoma cells. Disclosures: No relevant conflicts of interest to declare.

Antileukemic HLA-Restricted T-Cell Clones Generated With Naturally Processed Peptides Eluted From Acute Myeloblastic Leukemia Blasts

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Marina Ostankovitch ◽  
Agnès Buzyn ◽  
Delphine Bonhomme ◽  
Francine Connan ◽  
Didier Bouscary ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Acute Myeloblastic Leukemia ◽  
Peripheral Blood Mononuclear ◽  
T Cell Clones ◽  
Cell Clones ◽  
B7 Molecules ◽  
Blast Cells

Recent studies have shown that transfusions of HLA-compatible donor lymphocytes may induce complete remission in marrow-grafted patients with relapses of acute myeloblastic leukemia (AML). We investigated the in vitro generation of antileukemia T-cell clones obtained from the peripheral blood mononuclear cells of a partially HLA-compatible donor (HLA-A2 and B7 molecules in common with the leukemic blasts) after stimulation with a pool of naturally processed peptides extracted from leukemic blast cells collected at diagnosis from a patient with hyperleucocytosis AML. We recovered a significant quantity of peptides that bound to the HLA-A2 or HLA-B7 molecules that were able to induce cytolytic T-lymphocyte (CTL) lines and clones specific for the eluted AML peptides and restricted to the HLA-A2 or B7 molecules. Such CTL line did not recognize the patient's nonleukemic cells, and one clone was able to interact with the leukemic blasts from which the naturally processed peptides had been eluted. Such T-cell clones might provide a rationale for the development of adoptive immunotherapy and could be used to improve the efficiency of HLA-compatible T-lymphocyte transfusions and the graft-versus-leukemia response in patients with AML.

scholarly journals B7-1 or B7-2 Is Required to Produce the Lymphoproliferative Phenotype in Mice Lacking Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4)

1999 ◽  
Vol 189 (2) ◽  
pp. 435-440 ◽  
Author(s):  
Didier A. Mandelbrot ◽  
Alexander J. McAdam ◽  
Arlene H. Sharpe
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Activation ◽  
Lymphoproliferative Disease ◽  
Inhibitory Function ◽  
B7 Molecules

The costimulatory molecules B7-1 and B7-2 regulate T lymphocyte activation by delivering activating signals through CD28 and inhibitory signals through cytotoxic T lymphocyte–associated antigen 4 (CTLA-4). The importance of CTLA-4–mediated inhibition was demonstrated by the uncontrolled T cell activation and lymphoproliferative disease that develops in CTLA-4–deficient (−/−) mice. To examine the role of B7 signaling in the activation of CTLA-4–deficient T cells, we bred CTLA-4−/− mice with mice lacking B7-1, B7-2, or both B7 molecules. The CTLA-4/B7-1−/− and the CTLA-4/B7-2−/− mice develop lymphoproliferation and enhanced T cell activation. Mice lacking CTLA-4, B7-1, and B7-2 have a normal life-span, and do not have lymphocytic infiltrates in any organs, or increased T cell activation. Therefore, the two B7 molecules have overlapping functions, since either B7-1 or B7-2 alone can cause the CTLA-4−/− phenotype. Elimination of both B7-1 and B7-2 from the CTLA-4– deficient mouse abrogates the lymphocyte activation and disease, and does not reveal evidence for additional stimulatory CD28 ligands. The CTLA-4−/− phenotype can be reproduced with anti-CD28 antibody in mice lacking CTLA-4, B7-1, and B7-2, but wild-type mice are unaffected by the same treatment. This suggests that the inhibitory function of CTLA-4 can overcome strong CD28-mediated signaling in vivo.

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