ACTIVATION OF REGULATORY T CELLS BY ALPHA-MELANOCYTE STIMULATING HORMONE

摘要

The invention encompasses a method of down-regulating a T cell-mediated immu ne response, through activation or T cell receptor (TCR) stimulation of antigen - primed T cells in the presence of alpha-melanocyte stimulating hormone (.alpha.-MSH), which may be optionally enhanced by adding transforming growt h factor-.beta.2 (TGF-.beta.2) approximately 4-6 hours after the start of the primed T cells' exposure to .alpha.-MSH. Activation of the primed T cells ma y be mediated by presentation of the specific antigen to the primed T cells, o r by an anti-TCR antibody or a T cell mitogen. As a result of the .alpha.-MSH treatment modulating the T cell activation, antigen-specific, regulatory, CD4+/CD25+ T cells are generated that produce transforming growth factor- .beta. (TGF-.beta.) and can non-specifically down-regulate Th1-mediated inflammatory activities. The method may be used to down-regulate or suppress an autoimmune condition or a graft rejection in a transplant patient. The invention also encompasses a kit for generating regulatory T cell comprising a speciric antigen, .alpha.-MSH, and optionally, TGF-.beta.2 and/or a T cell culture medium. Also provided are gene therapy treatments for suppressing an autoimmune or graft rejection response, or for re-establishing autotolerance , by introducing genetic material (e.g. nucleic acid) for expressing .alpha.-M SH or a receptor-binding portion thereof, into a localized tissue site.