Immune regulation

Abstract

A method of regulating the immune system of a subject that involves removing antigen presenting cells from subject and loading preselected class II peptide fragments onto the subjects APC's outside the body of the subject.

1 . A method of regulating the immune system of a subject comprising: 
 providing antigen presenting cells (APC) from the subject;    loading preselected class II peptide fragments onto the subjects APC's outside the body of the subject;    introducing the loaded cells into the subject,    thereby regulating the immune response of the subject.    
     
     
         2 . The method of  claim 1 , comprising evaluating the extent to which the cells are loaded with the peptide.  
     
     
         3 . The method of  claim 1 , further comprising introducing a graft that expresses the preselected class II molecule into the subject.  
     
     
         4 . The method according to  claim 3 , wherein the graft is vascularized.  
     
     
         5 . The method of  claim 1 , wherein the preselected class II molecule is autogenic, allogenic, or xenogenic.  
     
     
         6 . The method of  claim 1 , wherein the tissue is autogenic, allogenic, or xenogenic.  
     
     
         7 . The method of  claim 1 , wherein the donor and recipient class II molecules match, or partially match.  
     
     
         8 . The method of  claim 1 , wherein the subject is human.  
     
     
         9 . The method of  claim 1 , wherein the MHC class II molecule and the MHC class II peptide are synthesized in the same cell.  
     
     
         10 . The method of  claim 1 , wherein the MHC class II peptide is processed by an endogenous pathway.  
     
     
         11 . The method of  claim 1 , wherein the regulating of the immune system comprises regulating T cells.  
     
     
         12 . The method of  claim 11 , wherein the T cells comprises autogenous T regulatory T cells and autogenous alloreactive cytotoxic T cells.  
     
     
         13 . The method of  claim 12 , wherein the thymic T regulatory T cells undergo thymic differentiation and peripheral T regulatory T cells undergo activation.  
     
     
         14 . The method of  claim 12 , wherein the alloreactive cytotoxic T cells undergo suppression.  
     
     
         15 . The method of  claim 12 , wherein the T regulatory cell population comprises CD4+CD25+ cells.  
     
     
         16 . A method of  claim 1 , wherein a nucleic acid encoding the class II protein to be presented as a fragment has been introduced into the APC.  
     
     
         17 . A method of  claim 16 , wherein the nucleic acid is expressed as a protein.  
     
     
         18 . The method of  claim 1 , wherein the method is used for graft survival.  
     
     
         19 . A method of  claim 18 , wherein the method is used as a treatment for a malady.  
     
     
         20 . A method of  claim 19 , wherein the malady is an autoimmune disease.  
     
     
         21 . A method of  claim 20 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, diabetes mellitus, multiple sclerosis, and lupis erythemotosis.sp? 
     
     
         22 . A method of  claim 1 , comprising suppressing alloreactive T cells in a subject by 
 administering donor MHC class II molecules to the subject wherein the donor MHC class II are processed to regulate T regulatory cells.    
     
     
         23 . A method of  claim 22 , comprising the administering is selected from the group consisting of: administering orally; introducing MHC class II molecules into syngeneic cells, into APC's, or administering donor-type class II+ lymphocytes, wherein the cells are introduced into a subject.  
     
     
         24 . The method of  claim 22 , wherein administering to the subject comprises administering to a subset of the subjects APC's.  
     
     
         25 . The method of  claim 24 , wherein the subset comprises dendritic cells.  
     
     
         26 . The method of  claim 25 , wherein the cells are immature dendritic cells.  
     
     
         27 . The method of  claim 26 , wherein the immature dendritic cells are bone marrow derived.  
     
     
         28 . The method of  claim 22 , wherein the subject comprises a patient receiving a graft. transplant.  
     
     
         29 . The method of  claim 22 , wherein the subject is human.  
     
     
         30 . An immune-complex of  claim 1 , comprising a peptide consisting of an amino acid sequence identical to that of a portion of a naturally occuring MHC class II molecule and a naturally occuring MHC class II heterodimer wherein the immune complex activates suppression of a subset of alloreactive T cells.  
     
     
         31 . A purified preparation of APC's having a Pep2Reg, e.g., as made by a method described herein.  
     
     
         32 . A preparation of APC's having exogenously added peptides which bind a membrane associated class II heterodimer and form a Pep2Reg complex.