Valpha24JalphaQ Receptor: Lead Diagnostic and Therapeutic for Type I Diabetes
Summary Background: Autoimmune diseases are the result of a patient's immune system attacking their own cells and tissues. This can result in a wide variety of diseases, including multiple sclerosis, myasthenia gravis, and type 1 diabetes. Researchers at Harvard University have discovered a novel method of diagnosing type 1 diabetes.
Invention: Type 1 diabetics lack the V?24J?Q receptor and express high amounts of the Th1 cytokine IFN-?. This discovery has important implications for early stage diagnosis and treatment of diseased individuals. For example, the number of V?24J?Q positive T cells as well their cytokine profile (see below) can be quantified to accurately reflect the stage of the disease. Additionally, the invention encompasses a novel method of treating type I diabetics by increasing the number of V?24J?Q positive T cells.
Applications Applications: A Diagnostic Method for Autoimmune Disease: The Number of V?24J?Q Positive T Cells: The diagnostic method involves determining the percentage of total T cells that are CD4-CD8-V?24J?Q+ and comparing these to the percentage of such cells in a control group of disease-free individuals. The likelihood of the tested individual having or developing an autoimmune disease increases as the percentage of CD4- CD8- V?24J?Q positive cells in this individual decreases relative to the percentage of these cells in the control group. One way that percentages may be determined is by sorting all CD4- CD8-?? TCR+ T cells using flow cytometry and amplifying V?24J?Q transcripts and sequencing the TCR CDR3 region of the amplified product in order to determine frequency of V?24J?Q. The frequency of V?24J?Q is multiplied by the percentage of total T cells that are CD4-CD8- V.alpha.24+. The method is compatible with other procedures as well. For example, antibodies specifically directed to a cell surface antigen exclusively present on V?24J?Q T cells may be used in standard immunoassays (radioimmunoassay or immunometric assays) for quantitation of cell number. This procedure may be applied to all autoimmune diseases, such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, myasthenia gravis, psoriasis, scleroderma, Sjogen's disease, and idiopathic thrombocytopenia purpura. A Diagnostic Method for Autoimmune Disease: Cytokines Secreted by CD4-CD8- V?24J?Q Positive T Cells: This diagnostic method involves determining the types of cytokines secreted by CD4-CD8-V?24J?Q+ T cells. CD4-CD- V?24J?Q+ T cells isolated from normal individuals and stimulated with a T cell activating factor such as anti-CD3 antibody secrete substantial levels of both IFN-? and interleukin-4 (IL-4). CD4-CD- V?24J?Q+ T cell isolated from patients with autoimmune disease preferentially secrete IFN-?. Thus, the method involves isolating cells from a test subject, determining the extent to which these cells secrete IL-4, and then correlating secretion with the likelihood of the subject having or developing an autoimmune disease. The likelihood of developing autoimmune disease decreases as the secretion of IL-4 increases. Alternatively, this method can also be performed by determining the ratio of IL-4 to IFN-? secretion in isolated CD4-CD- V?24J?Q+ T cells. In this case, the likelihood of an individual having or developing an autoimmune disease decreases as the ratio increases, i.e., as the levels of IL-4 rise with respect to the levels of IFN-gamma.
Publications: Wilson SB et al. Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes. Nature. 1998 Jan 8;391(6663):177-81. For Further Information Please Contact the Director of Business Development Laura Brass Email: firstname.lastname@example.org Telephone: (617) 495-3067
Strominger, Jack L.
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