ROLES OF JAK/STAT FAMILY MEMBERS IN TOLERANCE INDUCTION

摘要

The present invention relates to methods and compositions for reducing immune rejection, for example, transplant- or autoimmune disorder-related immune rejection. The present invention also relates to methods and compositions for monitoring transplant acceptance and for monitoring an autoimmune disorder in a subject mammal. The present invention still further relates to methods for identifying compounds that can reduce immune rejection. The present invention is based, in part, on the discovery, demonstrated herein, that immune rejection can be monitored by determining the amount of particular members of the Jak/Stat signal transduction pathway present within an affected tissue (that is, a transplant cell, tissue, organ, or organ system, or a cell, tissue, organ, or organ system that is, or is suspected of, being affected by an autoimmune disorder). The present invention is further based, in part, on the discovery, demonstrated herein, that immune rejection can be reduced and tolerance can be induced by modulating the amount of these particular members of the Jak/Stat signal transduction pathway present, expressed or active within an affected tissue. In particular, the results presented herein demonstrate that immune rejection can be monitored by determining the amount of Stat1 mRNA or protein, Stat2 mRNA or protein, Stat3 mRNA or protein, Stat4 mRNA or protein, Stat6 mRNA or protein, SOCS1 mRNA or protein, or SOCS3 mRNA or protein present, e.g., present in an affected tissue.