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 - 20 . (canceled) 
     
     
         21 . A method for assessing the risk of tumor progression in a subject comprising:
 (a) assaying a sample of tissue from a tumor or tumor draining lymph node from a subject for expression of indoleamine 2,3-dioxygenase (IDO); and   (b) correlating the risk of tumor progression to IDO expression in the tissue sample, wherein IDO expression is positively correlated with an increase in the risk of tumor progression.   
     
     
         22 . The method of  claim 21 , wherein IDO expression is assayed with use of an oligonucleotide probe that specifically hybridizes to IDO mRNA for the quantification of IDO expression in the sample. 
     
     
         23 . The method of  claim 21 , wherein IDO expression is assayed with use of an oligonucleotide probe that specifically hybridizes to IDO mRNA for the quantification of IDO expression by reverse transcriptase PCR. 
     
     
         24 . The method of  claim 21  further comprising assaying the sample of tumor tissue for the detection of one or more cell surface markers associated with high IDO expression. 
     
     
         25 . The method of  claim 24  wherein the one or more cell surface markers are selected from the group consisting of CD123, CD11c, and CCR6. 
     
     
         26 . The method of  claim 24  wherein the one or more cell surface markers are detected by and antibody or antibodies that recognize said one or more cell surface markers. 
     
     
         27 . The method of  claim 26  wherein the antibody or antibodies are directly labeled with a chemical, fluorescent, or an enzymatic moiety. 
     
     
         28 . The method of  claim 26  wherein the antibody or antibodies that recognize said one or more cell surface markers are further detected by the use of a labeled secondary antibody which recognizes the antibody or antibodies that recognize said one or more cell surface markers.