Costimulation Blockade in the Treatment of Rheumatic Diseases

  title={Costimulation Blockade in the Treatment of Rheumatic Diseases},
  author={Stamatis-Nick C. Liossis and Petros P. Sfikakis},
The autoimmune response is executed via cognate interactions between effector immune cells and antigen presenting cells. Cognate interactions provide the immune effectors with specific signals generated through the antigen receptor as well as with second, non-specific signals, generated from the interaction of pairs of cell-surface molecules (costimulatory molecules) present on their plasma membrane. Disruption of this second, non-specific costimulatory signal results in the interruption of the… 
Targeted Therapies in SLE
  • B. Hoyer, T. Dörner
  • Biology, Medicine
    Dubois' Lupus Erythematosus and Related Syndromes
  • 2019
Detection of Immune Checkpoint Receptors – A Current Challenge in Clinical Flow Cytometry
An overview of the detection of checkpoint molecules on immune cells in the peripheral blood and examples of a possible design of antibody panels are given.
Immunosuppression by Co‐stimulatory Molecules: Inhibition of CD2‐CD48/CD58 Interaction by Peptides from CD2 to Suppress Progression of Collagen‐induced Arthritis in Mice
In vivo studies indicated that peptide 6 was able to suppress the progression of CIA, and evaluation of the antigenicity of peptides in CIA and transgenic animal models indicated that this peptide is not immunogenic.
T cells interact with T cells via CD40-CD154 to promote autoimmunity in T1D
Data indicate that CD40 is an important signaling molecule on autoreactive CD4 T cells and contributes to their pathogenic effector function.
B cell therapies for rheumatoid arthritis: beyond B cell depletion.
Pharmacological Effects and Mechanisms of Action of Agents Blocking B Cells
The rationale for B cell therapies, the different strategies that can be used to target B cells and the mechanisms of action of drugs currently used for the treatment of autoimmune diseases are discussed.
Inflammation als Pathomechanismus in Atherosklerose und Adipositas
This review focuses on the diverse roles of the most established co-stimulatory molecules of the B7 and Tumor Necrosis Factor Receptor (TNFR) families, ie the CD28/CTLA4-CD80/CD86 and CD40L/CD40 dyads in the pathogenesis of atherosclerosis and obesity.
Regulation of atherosclerotic plaque inflammation
Targeting chemokines, leukotriene receptors and costimulatory molecules could represent potential therapeutic strategies to control atherosclerotic plaque inflammation.
[Biologics therapy for systemic lupus erythematosus. Current situation].
The monoclonal antibody against the cytokine BAFF/BLyS (belimumab) has been approved for the treatment of serologically active SLE and a number of other biologics against other cytokines are in the clinical development phase and appear to be promising for further improvement of the current therapeutic possibilities in SLE.


Treatment of murine lupus with CTLA4Ig.
In lupus-prone NZB/NZW filial generation mice, treatment with muCTLA4Ig blocked autoantibody production and prolonged life, even when treatment was delayed until the most advanced stage of clinical illness.
Adhesion and Costimulatory Molecules
T-cell inactivation or anergy is a major mechanism of subsequent tolerance in the peripheral lymphoid tissue and is defined as the inability of an organism to distinguish foreign from self.
CTLA 4 Ig inhibits T cell – dependent B-cell maturation in murine systemic lupus erythematosus
Costimulation-dependent cell-cell interactions within the germinal center lead to B-cell maturation through immunoglobulin isotype switching, somatic mutation, clonal expansion of high-affinity B cells, terminal differentiation to plasma cells, and formation of memory B cells that express B7 and can further activate T cells by acting as APCs.
The relative contribution of the CD28 and gp39 costimulatory pathways in the clonal expansion and pathogenic acquisition of self-reactive T cells
It is shown that autoimmune disease and autoantibody production are inhibitable by blocking either the gp39 or the CD28 pathway, whereas inhibition of clonal expansion of the effector T cell population occurs only when both pathways are blocked.
Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation
It is reported here that the ligand of PD-1 (PD-L1), an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells, is a member of the B7 gene family.
CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB x NZW F1 mice.
It is shown that lupus-prone NZB x NZW F(1) mice given three injections of anti-CD137 (4-1BB) mAb's between 26 and 35 weeks of age reversed acute disease, blocked chronic disease, and extended the mice's lifespan from 10 months to more than 2 years, supporting the hypothesis that CD137-mediated signaling anergized CD4(+) T cells during priming at the DC interface.
Effects of anti-CD154 treatment on B cells in murine systemic lupus erythematosus.
Anti-CD154 is a B cell-depleting therapy that affects multiple B cell subsets and autoreactive B cells progress through a series of activation steps before they become fully competent antibody-producing cells, and the general immunosuppression induced during treatment will need to be taken into account.
Collagen-induced arthritis in the BB rat. Prevention of disease by treatment with CTLA-4-Ig.
CTLA-4-Ig treatment prevents clinical and histological manifestations of disease in a collagen-induced arthritis model of rheumatoid arthritis in the diabetes resistant BB/Wor rat, when therapy is initiated before immunization with bovine type II collagen (BIIC).
Inducible costimulator is essential for collagen-induced arthritis.
It is found that ICOS knockout mice on the DBA/1 background were completely resistant to collagen-induced arthritis and exhibited absence of joint tissue inflammation, suggesting novel means for treating patients with rheumatoid arthritis.
CTLA4Ig inhibits T cell-dependent B-cell maturation in murine systemic lupus erythematosus.
It is shown that CTLA4Ig has a beneficial effect on murine SLE for as long as it is present in the serum, and is associated with decreased expansion of both the IgM and IgG autoreactive B-cell population, inhibition of immunoglobulin class switching, decreased frequency and altered pattern of somatic mutation, and a marked decrease in the numbers of activated CD4-positive T cells.