Getting a grip on antigen-specific CD4 T cells: Tracking autoimmune T cells in vivo

Extract: Autoreactive T cells are part of the normal immune system and are kept under control by mechanisms known as anergy. Autoimmune diseases are caused by the breakdown of this tolerance, and T cell activation leads to severe inflammation and tissue damage. For example, in rheumatoid arthritis, synovial joints will be destroyed whereas in insulin-dependent diabetes mellitus (IDDM, type 1 diabetes), insulin-producing beta cells in the pancreatic islets of Langerhans will be the focus of the attack. The genetic makeup of susceptible individuals and the environmental factors leading to autoimmunity are complex and largely unknown. In many instances, the main genetic locus that has been determined is the MHC (major histocompatibility complex) class II locus. In the case of IDDM this locus encodes alleles such as HLA-DR4, -DR3, and -DQ8 in humans and I-Ag7 in the non-obese diabetic (NOD) mouse. Since MHC class II molecules present peptides to CD4 positive T cells, it is tempting to link genes and function and to study closely CD4+ T cells in the context of autoimmunity. It is now well established that, indeed, these cells are essential for the initiation and development of autoimmunity, however, in-depth investigation of them has been impeded by two major roadblocks. First, potential antigens, and therefore relevant peptides, are scarce and difficult to isolate. Secondly, reagents able to detect T cells in an antigen-specific fashion have remained elusive.