Discovery of regulatory t cells programmed to suppress an immune response

Abstract

A method to treat an autoimmune disease is provided. The method involves administration of interleukin-15 receptor (IL-15R) agonists in an amount effective to ameliorate a symptom of the autoimmune disease. The invention also involves a method to treat an autoimmune disease by ex-vivo expansion of CD44+CD122+Kir+ CD8+ Treg cells and administration of the CD44+CD122+Kir+ CD8+ Treg cells. Compositions comprising CD44+CD122+Kir+ CD8+ Treg cells are also provided. Methods for stimulating an immune response to an antigen are also provided.

Description

RELATED APPLICATIONS[0001]This application claims the benefit under 35 U.S.C. §119(e) of U.S. provisional application Ser. No. 61 / 405,696, filed Oct. 22, 2010, the content of which is incorporated by reference herein in its entirety.FEDERALLY SPONSORED RESEARCH[0002]This invention was made with Government support under NIH Grant AI 037562. Accordingly, the Government has certain rights in this invention.BACKGROUND OF THE INVENTION[0003]Achieving a balance between induction of protective immunity against pathogens and maintenance of self-tolerance is a central feature of the adaptive immune system. Although negative selection in the thymus removes the majority of clones that express T cell receptors (TCR) with high affinity for self-peptide MHC products, this process is incomplete. A significant fraction of mature peripheral T cells that respond to self-peptide-MHC complexes may differentiate into effector cells in the context of inflammatory stimuli (Bouneaud et al., 2000; Goldrath ...

AI Technical Summary

Benefits of technology

The patent is about a new method for treating autoimmune diseases by using a specific type of immune cell called CD8+ cells. These cells are enriched in a population of cells and can be administered to patients to help treat the symptoms of the disease. The method involves isolating these cells from the patient and growing them in a culture medium with specific proteins to increase their number. The CD8+ cells are then administered to the patient in a therapeutic amount. This method can be used to treat a variety of autoimmune diseases such as lupus erythematosus, rheumatoid arthritis, and insulin-dependent diabetes mellitus.

Problems solved by technology

Although negative selection in the thymus removes the majority of clones that express T cell receptors (TCR) with high affinity for self-peptide MHC products, this process is incomplete.

Although this process is constrained by abortive or defective TCR signaling resulting in cellular elimination (AICD) or inactivation (Martin et al., 1999; Kearney et al., 1994), these cell-intrinsic mechanisms may not suffice to prevent the development of autoimmune disorders (Anderton et al., 2001; Panoutsakopoulou et al., 2001).

However, regulatory T cells that are genetically programmed to inhibit development of autoantibody formation and autoimmune diseases have not been defined.

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