Antigen-presenting cell populations and their use as reagents for enhancing or reducing immune tolerance

Abstract

The present invention is based on the discovery antigen-presenting cells (APCs) may be generated to have predetermined levels of expression of the intracellular enzyme, indoleamine 2,3-dioxygenase (IDO). Because expression of high levels of IDO is correlated with a reduced ability to stimulate T cell responses and an enhanced ability to induce immunologic tolerance, APCs having high levels of IDO may be used to increase tolerance in the immune system, as for example in transplant therapy or treatment of autoimmune disorders. For example, APCs having high levels of IDO, and expressing or loaded with at least one antigen from a donor tissue may be used to increase tolerance of the recipient to the donor's tissue. Alternatively, APCs having reduced levels of IDO expression and expressing or loaded with at least one antigen from a cancer or infectious pathogen may be used as vaccines to promote T cell responses and increase immunity.

1 . An isolated population of immunosuppressive dendritic APCs wherein said dendritic APCs express IDO, CD1c and CD123 wherein said dendritic APCs are able to suppress T cell proliferation. 
     
     
         2 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein said dendritic APCs further express one or more of CCR6, CD83, and CD11b. 
     
     
         3 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein said dendritic APCs further express CCR6. 
     
     
         4 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein said dendritic APCs further express CD83. 
     
     
         5 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein said dendritic APCs further express CD11b. 
     
     
         6 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein said dendritic APCs further express two or more of CCR6, CD83, and CD11b. 
     
     
         7 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein said dendritic APCs further express CCR6 and CD83. 
     
     
         8 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein said dendritic APCs further express CCR6 and CD11b. 
     
     
         9 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein said dendritic APCs further express CD83 and CD11b. 
     
     
         10 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein the dendritic APCs do not express BDCA-2. 
     
     
         11 . The isolated population of immunosuppressive dendritic APCs of any one of  claims 2 - 9  wherein the dendritic APCs do not express BDCA-2. 
     
     
         12 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein the dendritic APCs do not express CD14. 
     
     
         13 . The isolated population of immunosuppressive dendritic APCs of any one of  claims 2 - 9  wherein the dendritic APCs do not express CD14. 
     
     
         14 . The isolated population of immunosuppressive dendritic APCs of  claim 1  wherein the dendritic APCs do not express CD14 or BDCA-2. 
     
     
         15 . The isolated population of immunosuppressive dendritic APCs of any one of  claims 2 - 9  wherein the dendritic APCs do not express CD14 or BDCA-2. 
     
     
         16 . An isolated population of immunosuppressive dendritic APCs wherein said dendritic APCs express IDO, CD11c, CD123, CD83, CCR6 and CD11b wherein said dendritic APCs do not express CD14, BDCA-2 and wherein said dendritic APCs are able to suppress T cell proliferation.