Type 1 diabetes is unusual among autoimmune diseases because diagnosis is greatly aided by laboratory tests. Levels of blood sugar and glycosylated hemoglobin are excellent measures of disease progression. The symptoms of disease are treated with insulin, which would normally be produced by the pancreatic beta cells that are destroyed in the autoimmune process. In common with other autoimmune diseases, the cause of type 1 diabetes is not known, though insulin itself has been a leading candidate autoantigen. Here, Kent and colleagues show they could find insulin-specific T lymphocytes in the lymph nodes draining the pancreas in 2 long-term diabetics, but not in 3 non-diabetic individuals or 1 recently-diagnosed diabetic. They argue against the T cells having been stimulated by therapeutic insulin because none were found in the spleen of one diabetic. They convincingly demonstrate that the T cell response is specific for the insulin peptide (residues 1-15 of the A chain) bound by host histocompatibility molecules (HLA-DR). The insulin-specific T cells were helper (CD4+) cells and, curiously, secreted a suspected tolerogenic helper type 2 cytokine (interleukin-13) and not a proinflamatory helper type 1 cytokine (interferon-gamma) in vitro. These observations strengthen the argument that long-term diabetes correlates with increased immune reactivity against
insulin.
Kent et al., Nature, May 12, 2005. 435(7039):224-8.
Sunday, January 21, 2007
Insulin-Specific T Cells in Long-Term Diabetics
Subscribe to:
Post Comments (Atom)
1 comment:
Duh
Of course the T cells from the normal subjects did not proliferate in response to the insulin peptide. The insulin peptide used in this report binds HLA-DR molecules expressed by the long-term diabetic patients, DR3 and DR4. The normal subjects and the recently-diagnosed patient expressed a number of different DR molecules, including DR1, DR2, DR9, and DR11. Only one normal subject expressed one DR4 allele and none expressed DR3. A true test of the specificity would begin with determining which insulin peptide bind to these diverse DR molecules.
On a separate note, isn't it odd that no insulin-specific T cells could be detected in the recently-diagnosed diabetic? If insulin-specific T cells are triggering the immune response, then draining lymph nodes would seem to be the most likely source. The insulin-specific T cells in the long-term diabetics might result from, not cause, the chronic immune destruction of the beta cells.
Post a Comment