Rheumatoid Arthritis: Dazzi F

Tyndall A, Dazzi F. · Department of Rheumatology, University of Basel, Felix Platter Spital, Burfelderstrasse 101, 4012 Basel, Switzerland. · Best Pract Res Clin Haematol. · Pubmed #18503993 No free full text.

Abstract: Many of the clinical, histological and serological manifestations of chronic graft-versus-host disease (GVHD) resemble autoimmune disease (AD), and although the differences are significant, they may be more semantic than biological. Indeed, studies suggest that some ADs may represent a fetal-versus-maternal chronic GVHD. Both conditions involve dysregulated immune responses resulting in tissue inflammation, damage, scarring and organ dysfunction, and both may be associated with a genetic predisposition. Epitope-specific autoaggressive phenomena such as immune thrombocytopenic purpura (ITP) are often seen following allogeneic hematopoietic stem-cell transplantation (HCT), implying a loss of specific tolerance to self structures. However, the more widespread manifestations of GVHD such as the well-known scleroderma-like symptoms differ in many fundamental respects from de-novo scleroderma, and other multisystem ADs such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).

Dazzi F, Horwood NJ. · Stem Cell Biology Section, Kennedy Institute of Rheumatology and Division of Investigative Sciences, Imperial College, London, UK. · Curr Opin Oncol. · Pubmed #17906466 No free full text.

Abstract: PURPOSE OF REVIEW: Mesenchymal stem cells have the capacity to differentiate into several mesenchymal tissues, including the components of the hematopoietic stem cell niche. Mesenchymal stem cells also exhibit a powerful immunosuppressive activity. Here we review the most recent data to identify the properties of therapeutic significance. RECENT FINDINGS: Mesenchymal stem cells are attractive not only in regenerative medicine but also for the treatment of autoimmune diseases and graft-versus-host disease. Initial experience in animal models and the clinical setting have produced very encouraging results whereby mesenchymal stem cells have been shown to accelerate recovery after myocardial infarction, improve growth velocity in children with osteogenesis imperfecta, and ameliorate severe graft-versus-host disease as well as, in mouse models, rheumatoid arthritis and multiple sclerosis. Their use in the clinical setting, however, must be considered with caution because there is evidence that mesenchymal stem cells may also contribute to the maintenance of cancer stem cells. SUMMARY: The interest generated by mesenchymal stem cells has rapidly favored several initiatives to test their therapeutic potentials. There is still much to investigate to characterize their phenotype, understand their mechanisms of action, and optimize their in-vitro expansion for clinical use.

Tyndall A, Walker UA, Cope A, Dazzi F, De Bari C, Fibbe W, Guiducci S, Jones S, Jorgensen C, Le Blanc K, Luyten F, McGonagle D, Martin I, Bocelli-Tyndall C, Pennesi G, Pistoia V, Pitzalis C, Uccelli A, Wulffraat N, Feldmann M. · Rheumatology, University Hospital Basel, Felix Platter Spital, Burgfelderstrasse 101, Basel, CH-4012, Switzerland. · Arthritis Res Ther. · Pubmed #17284303 links to  free full text

Abstract: Multipotent mesenchymal stromal cells isolated from bone marrow and other sites are currently being studied to determine their potential role in the pathogenesis and/or management of autoimmune diseases. In vitro studies have shown that they exhibit a dose-dependent antiproliferative effect on T and B lymphocytes, dendritic cells, natural killer cells and various B cell tumour lines--an effect that is both cell contact and soluble factor dependent. Animal models of autoimmune disease treated with multipotent mesenchymal stromal cells have mostly exhibited a positive clinical response, as have a limited number of patients suffering from acute graft versus host disease. This review summarizes the findings of a 1-day meeting devoted to the subject with the aim of coordinating efforts.

Zhang Z, Gorman CL, Vermi AC, Monaco C, Foey A, Owen S, Amjadi P, Vallance A, McClinton C, Marelli-Berg F, Isomäki P, Russell A, Dazzi F, Vyse TJ, Brennan FM, Cope AP. · Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, Hammersmith, London, United Kingdom. · Blood. · Pubmed #17255353 links to  free full text

Abstract: The T-cell receptor zeta (TCRzeta) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRzeta expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRzeta expression and effector function in T cells. We report here that TCRzeta(dim) lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRzeta(bright) counterparts, TCRzeta(dim) cells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCRzeta(dim) T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRzeta(dim) T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRzeta(dim) T cells make them promising cellular targets for the treatment of chronic inflammatory disease.