Causes of Scleroderma: B Cells and T Cells

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Cause of Scleroderma: B Cells and T Cells

Overview of B Cells and T Cells
B Cells and T-Cells and Autoimmunity

B Cells and T Cells and Systemic Sclerosis

Overview of B Cells and T Cells

T cells are white blood cells that help stimulate an immune response to infections. In the thymus gland, lympohocytes are matured into T cells. Sometimes T cells become overactive, which is suspected as being part of the process that leads to autoimmune diseases.

B Cells and T Cells.The white blood cells involved in the acquired immune response are called 'lymphocytes'. There are two main types of lymphocytes - B cells and T cells. B and T lymphocytes are made in the bone marrow, like the other blood cells. They have to fully mature before they can help in the immune response. T cells travel through the blood stream to the thymus gland where they become fully developed. Once they are fully mature, they travel to the spleen and lymph nodes, ready to fight infection. Cancer Research UK.

A protein known as H2-DM may help regulate T cells, so studies are underway with genetically altered mice to investigate the potential links between H2-DM and T cells.

Thymus. The thymus is a ductless gland located in the upper anterior portion of the chest cavity. It is most active during puberty, after which it shrinks in size and activity in most individuals and is replaced with fat. The thymus plays an important role in the development of the immune system in early life, and its cells form a part of the body's normal immune system. Wikepedia.

T cells and B cells in the pathogenesis of systemic sclerosis: recent insights and therapeutic opportunities. Understanding the interplay between T and B cells, and the processes that promote the fibrotic cytokine pattern seen in these patients is of utmost importance for the development of effective therapies to treat the clinical complications. PubMed. Curr Rheumatol Rep. 2006 Apr;8(2):123-30.

B Cell Targeted Therapies in Autoimmune Diseases. In addition to rheumatoid arthritis, B cells are likely to play a significant role in the development of other autoimmune rheumatic diseases, such as systemic lupus erythematosus, myositis, and vasculitis. J Rheumatol 2006 May;33 Suppl 77: 24-28. (Also see: Lupus, Dermatomyositis, and Vasculitis)

Gene Critical To Activation Of Infection-Fighting Immune Cells Identified By Weill Cornell. While the potential for KLHL6-enhancing agents isn't yet known, they might someday prove beneficial against a number of viral or bacterial illnesses, including HIV/AIDS. That's why the discovery of a gene that's key to B-lymphocyte activation is so important. Medical News Today. 04/03/06.

Monoclonal Antibody: Immune Therapy Could Treat Leukemias, Autoimmune Diseases, Transplant Rejection. In studies with mice, treatment with a new monoclonal antibody that targets immune system B cells has shown considerable promise for treating leukemias, autoimmune diseases and transplant rejection, according to immunologists at Duke University Medical Center. ScienceDaily. 10/13/05.

B Cells and T Cells and Autoimmunity

Autoimmune Disease Treatment May Not Dampen Immune System. Researchers have uncovered cellular proteins that may be key to certain autoimmune and inflammatory diseases. The findings, performed so far only in mice, point to potential new treatments for a range of human diseases that are mediated by immune system T-cells. Such a treatment might provide all the benefits of existing drugs, without the general immune suppression that often accompanies them. Jeffrey Perkel. MedicineNet.com. 06/19/08.

Cell Surface Receptors Are All 'Talk' In T Cell Stimulation. Understanding the mechanisms that drive healthy immune responses is important when it comes to combating autoimmune diseases, which occur when cells that should attack invading organisms turn on the body instead. ScienceDaily. 06/13/08.

B Cell Mutations That May Cause Cancers And Autoimmune Diseases. B cells, the white blood cells that produce antibodies, form a key part of our 'immune response'. We must maintain exactly the right number of B cells to remain healthy. Medical News Today. 03/03/08. (Also see: Autoimmunity)

Association of autoantibodies with Ku and DNA repair proteins in connective tissue diseases. The presence of autoantibodies directed against macromolecular complexes known to play roles in the DNA damage response provides evidence that B-cell responses to latent or persistent DNA damage may be present at the onset or during the development of autoimmunity in certain systemic autoimmune rheumatic diseases. Rheumatology 2008 47(2):165-171.

Triggering the autoimmune response against islets in type 1 diabetes. The authors found that transplanted islet cells, but not bone marrow cells, expressing native B16:Y insulin (tyrosine at position 16 of insulin B chain) restored anti-insulin autoimmunity in mice that lacked native insulin genes. SpiritIndia.com. July 2007. (Also see: Diabetes)

Researchers Identify a Potential Role For Retinoic Acid In Autoimmune And Inflammatory Diseases Identified. An important finding, which could eventually lead to a new therapeutic approach for treating autoimmune and inflammatory diseases such as rheumatoid arthritis, colitis, psoriasis and others. The studies, conducted in laboratory mice, demonstrated the role of retinoic acid, a substance derived when Vitamin A is broken down in the body, in regulating inflammation. EurekAlert!. 06/1407. (Also see: Autoimmunity)

Immunization Against Type 1 Diabetes - Mice Successfully Treated. Researchers in Toulouse (France) and Berlin-Buch have successfully treated type 1 diabetic mice with a vaccination. The researchers showed that, in principle, it is possible to treat autoimmune diseases by inducing "active tolerance". That means activating the immune system so that it no longer attacks the body's own structures, but instead protects them from the immune attack. Medical News Today. 05/24/07. (Also see: Diabetes)

Complement receptor 3 sends a signal to dampen the immune system. Researchers reported that complement receptor 3 (CR3), a protein found on cell surfaces, inhibits dendritic cells, the sentinels of the immune system, from setting off an alarm signal that brings on a full immune response. News-Medical.Net 05/16/07. (Also see: Dendritic Cells)

Glucosamine-like dietary supplement suppresses autoimmune response in multiple sclerosis and type-1 diabetes mellitus. A glucosamine-like dietary supplement has been found to suppress the damaging autoimmune response seen in multiple sclerosis and type-1 diabetes mellitus, according to Univerisity of California, Irvine health sciences researchers. News-Medical Net. 05/16/07. (Also see: Diabetes, and MS)

Researchers discover connection between allergic diseases and autoimmune diseases. Our study implies that allergic and inflammatory diseases may actually trigger autoimmune diseases by relaxing the controls that normally eliminate newly produced, self-reactive B cells. PhysOrg.com (Nature Immunology) April 3 2007. (Also see: Autoimmunity)

Saving Your Self From Yourself. Being able to better tune the body's defenses offers the possibility of a wide range of novel therapies to treat diseases like arthritis and diabetes, to combat transplant rejection, and, perhaps, to fight cancer. In autoimmune diseases, T cells attack the self, rather than the non-self. Harvard University Gazette. 02/08/07. (Also see: Natural Killer Cells)

Scientists Learn The Origin Of Rogue B Cells. Researchers have provided some new clues into one likely factor for the immune system turning against parts of the body it is designed to protect, leading to autoimmune disease: the early development of immune system cells called B cells. Medical News Today. 02/11/07.

B Cell Reconstitution After Rituximab Recapitulates B Cell Ontogeny with a Preponderance of Transitional B cells and a Paucity of Memory B Cells. These results suggest fundamental differences in the B cell depletion and/or reconstitution process experienced by different groups of patients that impact clinical and immunologic outcomes. Jennifer H. Anolik. 1974 ACR 2006. (Also see: Medications)

Bone and Intestinal Disease May Have Common Cause. In studies with mice, scientists have found evidence that osteoporosis-like bone disorders and inflammatory intestinal disorders are both caused by the abnormal regulation of a common protein. PakTribune. 12/28/06. (Also see: Bowel Dysfunction)

Molecule linked to autoimmune disease relapses identified at Stanford. The study lays the groundwork for a way to determine when a relapse is about to occur, and could eventually lead to a treatment to prevent relapses. SpiritIndia.com. Dec 06. (Also see: Multiple Sclerosis)

Autoimmune disease triggered if T cells miss a single protein early on. The discovery suggests that effective strategies to treat autoimmune disease should target not only the "peripheral" sites where autoimmune disease is active, but also the thymus, the organ where T cells and self-proteins, or self-antigens, first interact. EurekAlert! 11/21/06. (Also see: Diabetes)

Natural compounds block autoimmune response in diabetes, arthritis. Natural compounds from a sea anemone extract and from the rue shrub plant block autoimmune disease responses in both type 1 diabetes and rheumatoid arthritis, U.S. researchers report. EurekAlert! University of California, Irvine. 11/06/06. (Also see: Diabetes and Rheumatoid Arthritis)

How The Immune System Avoids Attacking Itself. A finding by University of Pennsylvania School of Medicine researchers about how immune cells "decide" to become active or inactive may have applications in fighting cancerous tumors, autoimmune diseases, and organ transplant rejection. ScienceDaily. 10/17/06.

B-Lymphocyte Depletion Reduces Skin Fibrosis and Autoimmunity in the Tight-Skin Mouse Model for Systemic Sclerosis. B-cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance. American Journal of Pathology. 2006;169:954-966. (Also see: Skin Fibrosis)

T-Cell Costimulation — Biology, Therapeutic Potential, and Challenges. CTLA-4 is involved in the induction and maintenance of T-cell tolerance. CTLA-4 polymorphisms in humans have been linked to susceptibility to autoimmune diseases, including type 1 diabetes and autoimmune thyroid disease. The New England Journal of Medicine. Vol 355:973-975,10. 09/07/06. (Also see: Diabetes and Thyroid Disease)

Importance of T cells in the prevention of autoimmune diseases. Researchers found that healthy individuals have up to twice the number of disease-fighting regulatory T cells compared with Irritable Bowel Disease patients at the onset of disease. News-Medical.net 07/09/06. (Also see: Gastrointestinal Involvement)

New Tool Can Boost or Block the Body's Protective Inner Barriers. A chemical tool allows scientists to manipulate control of the passage of substances through the barriers between blood and the tissues of every organ. NIH News. 07/13/06.

Antibody-interleukin Complexes Stimulate Immune Responses, New Study Shows. The findings could be significant for developing new ways to help patients with autoimmune diseases. The study showed that different cytokine-antibody complexes such as IL-2/IL-2 mAb could be clinically useful to selectively boost or inhibit the immune response in vivo. Medical News Today 02/26/06.

Pathogenic autoantibodies: Emerging insights into tissue injury. Accumulating evidence is emerging that B lymphocytes and autoantibodies are critical in the development of autoimmune disease. Studies of autoantibodies penetrating living cells suggest a dosage effect in generating a biological outcome in vivo. PubMed 02/28/06. (Also see: Antibodies)

Mechanisms of lymphocyte migration in autoimmune disease. The recruitment of leukocytes to inflamed tissues plays an essential role in combating infection and promoting wound healing. However, in autoimmune diseases such as multiple sclerosis and diabetes, leukocytes enter tissues and contribute to inappropriate inflammatory responses, which cause tissue injury and dysfunction. PubMed. Tissue Antigens. 2005 Sep;66(3):163-72.

Target identification and validation in systemic autoimmunity. Recent genome-based approaches to autoimmunity, have revealed novel pathogenic targets, including genes that negatively regulate T- and/or B-cell effector differentiation, as well as genes that specifically regulate T- cell-B-cell collaboration. PubMed. Immunol Res. 2005;32(1-3):201-10. (Also see: Causes of Scleroderma: Genetics)

Immune receptor signaling, aging, and autoimmunity. With advancing age, the immune system undergoes changes that predispose to autoimmune reactivity. Self-antigens acquire alterations that increase their immunogenicity. PubMed. Cell Immunol. 2005 Jun 2.

UV-induced regulatory T cells. Ultraviolet (UV) radiation suppresses the immune system in antigen-specific fashion. This effect is mediated by UV-induced regulatory T cells. The further characterisation of these cells will determine whether they can be applied in the future therapeutically with the ultimate aim to induce specific immunosuppression. PubMed. J Dtsch Dermatol Ges. 2005 Jul;3(7):504-10.

New Insight Into Autoimmune Disease: Bacterial Infections Promote Recognition of Self-glycolipids. The development of certain autoimmune diseases may be associated with a bacterial or viral infection that stimulates production of antibodies and immune cells called T cells, which are targeted against bacterial proteins that closely resemble "self" proteins, leading to crossreactivity with healthy tissues. RedOrbit News. 06/21/05.

Pathogenesis of systemic sclerosis: Altered B cell function is the key linking systemic autoimmunity and tissue fibrosis. Augmented cytokine production by B cells is a potential candidate for the induction of skin sclerosis. Alternatively, B cells may influence tissue fibrosis by regulating T cell activation and cytokine production through their antigen-presenting and co-stimulatory abilities. Thus, altered B cell function may result in tissue fibrosis, as well as autoimmunity, in SSc. PubMed. J Dermatol Sci. 2005 May 7.

Regulation of immunity by self-reactive T cells. Subpopulations of self-reactive T cells have a strong influence on self tolerance and may represent targets for therapeutic intervention to control a variety of autoimmune diseases, tumour growth and infection. PubMed. Nature. 2005 Jun 2;435(7042):598-604.

Evidence that Pregnancy Specific Glycoproteins Regulate T-Cell Function and Inflammatory Autoimmune Disease During Pregnancy. Many T-cell mediated autoimmune disorders, including multiple sclerosis (MS) are suppressed during pregnancy. The regulation of T-cell function during pregnancy is likely the result of significant hormonal changes and may well involve immunoregulatory proteins derived from the placenta. PubMed. Curr Drug Targets Inflamm Allergy. 2005 Apr;4(2):231-7. (Also see: Pregnancy and Scleroderma and Multiple Sclerosis)

Scientists discover way to control allergic reactions by increasing numbers of CD4+ regulatory T-cells. This discovery could also have implications for autoimmune diseases. Autoimmune diseases arise when too many T-helper 1 cells are produced against one's own body. With this approach, it may be possible to stop or limit these diseases. i-Newswire.com 04/12/05.

GITR: a multifaceted regulator of immunity belonging to the tumor necrosis factor receptor superfamily. GITR (Glucocorticoid-induced TNFR-related gene) activation causes development of autoimmune diseases and restores immune responses in a persistent retroviral infection model and in a tumor model. The GITR-GITRL system appears crucial in regulating immunity and warrants further study. PubMed. Eur J Immunol. 2005 Mar 15;35(4):1016-1022.

Reduced Circulating Natural Killer T Cells and γ/δ T Cells in Patients with Systemic Sclerosis. Impairment of NK-T cells and of T cells expressing γ/δ TCR may lead to downregulation of normal immune response, and seems to be important for immunological and inflammatory aspects of SSc. J. Rheumatol No. 2 February 2005;32:283-6.

B and T Cells and Systemic Sclerosis (SSc, Scleroderma)

The Immunobiology of Systemic Sclerosis. The SSc hallmarks of vascular damage, immunologic activation, and collagen deposition can be traced to 4 major factors: T-cells, fibroblasts, B-cells, and cytokines/chemokines. Significant variations in laboratory data among patients suggest that the pathology reflects a heterogeneous disease. (Science Direct) Seminars in Arthritis and Rheumatism . 02/13/08. (Also see: Causes of Scleroderma, Fibroblasts, and Cytokines))

Resistance to Apoptosis in Circulating a/ß and g/d T Lymphocytes from Patients with Systemic Sclerosis (SSc). Resistance to apoptosis is present in a/b and g/d T cell lymphocyte subsets of patients with SSc, and several pathways seem to be connected in this setting. J Rheumatol 2006 October;33:2003-14.

Prolactin synthesis by lymphocytes from patients with systemic sclerosis. Lymphocytes might contribute to elevated prolactin levels in patients with SSc and these cells themselves may be sensitive to prolactin stimulation. Therefore, a pharmacologic attempt to lower prolactin levels in patients with SSc could proof beneficial. PubMed. Biomed Pharmacother. 2006 Mar 3. (Also see: Causes of Scleroderma: Hormones)

Elevated Numbers of Microparticles in the Blood of Patients with Systemic Sclerosis. We show here for the first time that the numbers of microparticles in the blood of patients with SSc is increased and that the major fraction of microparticles is derived from platelets. Since microparticles have been shown to have a dramatic effect on cell activation, the role of microparticles in SSc has to be further investigated. Serena Guiducci. 1207. ACR 2005.

The presence of dominant T-cell clones in peripheral blood of patients with collagen vascular disorders. The presence of a dominant T-cell clone in peripheral blood is significantly more frequent in collagen vascular disorders than in controls, especially in patients with scleroderma, whatever the clinical subset. PubMed. Br J Dermatol. 2006 Mar;154(3):445-9.

B lymphocytes and systemic sclerosis. B cells may have more pathogenic roles in systemic sclerosis than had been appreciated. Collectively, B cells and B-cell-specific response regulators such as CD19/CD22 appear to be potential therapeutic targets of the disease. PubMed. Curr Opin Rheumatol. 2005 Nov;17(6):746-51. (Also see: Dr. Shinichi Sato)

Thymus alterations and systemic sclerosis. The relationship of thymus alterations with shorter disease duration, as well as with serum anti-Scl70, suggests that thymic dysfunction could play a pathogenetic role mostly in the early phases of the disease, and possibly in specific SSc patient subsets. PubMed. Rheumatology (Oxford). 2005 Sep 27.

Early T cell activation in the skin from patients with systemic sclerosis. The expression of early T cell activation antigen CD69 in skin lesions suggests that T cells may actively participate in cell-cell contact with fibroblasts to promote fibrosis. PubMed. Ann Rheum Dis. 2005 Aug;64(8):1233-5.

New developments in the pathogenesis of systemic sclerosis. Recent studies have suggested that the activation of the immune system is of paramount importance in the pathogenesis of SSc. T Cells are activated by antigen, infiltrate early the skin lesions in SSc, and produce the profibrotic cytokine IL-4, and are also required for autoantibody production. PubMed. Autoimmunity. 2005 Mar;38(2):113-6.

A human T-cell lymphotropic virus type-1 (HTLV-1) carrier complicated with various autoimmune diseases including primary biliary cirrhosis. A 47-year-old woman diagnosed as having overlap syndrome with scleroderma, systemic lupus erythematosus and possible polymyositis associated with primary biliary cirrhosis. (The tests) suggest the possibility of a relationship between HTLV-1 infection and various autoimmune disorders including primary biliary cirrhosis. PubMed. Hepatol Res. 2005 Feb 7. (Also see: Overlap Syndrome, Liver Involvement, Lupus, Polymyositis and Scleroderma)

Clonal T cells in the blood of patients with systemic sclerosis. Clonally expanded T cells were more commonly detected in patients with limited cutaneous sclerosis than in those with diffuse cutaneous sclerosis, which is also in accordance with a possible role of clonal T cells in patients with limited cutaneous sclerosis. PubMed. Arch Dermatol. 2005 Jan;141(1):88-9. (Also see: Limited Scleroderma)

T cell repertoire in patients with stable scleroderma. At onset of systemic sclerosis (SSc), T cells have been found to oligoclonally expand in the skin, presumably in response to auto-antigens, but the T cell repertoire has not been evaluated at a later stage. Findings suggest that antigen-driven immune responses may play a lesser role in established SSc than at disease onset. PubMed. Clin Exp Immunol. 2005 Feb;139(2):348-54.