| First Author | Maric M | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 2 | Pages | 746-50 |
| PubMed ID | 19124716 | Mgi Jnum | J:143502 |
| Mgi Id | MGI:3827045 | Doi | 10.4049/jimmunol.182.2.746 |
| Citation | Maric M, et al. (2009) Cutting edge: developmental up-regulation of IFN-gamma-inducible lysosomal thiol reductase expression leads to reduced T Cell Sensitivity and less severe autoimmunity. J Immunol 182(2):746-50 |
| abstractText | Reactivity to self-peptide/MHC complexes is required for selection of the TCR repertoire in the thymus but can also promote autoimmunity. Reduced TCR sensitivity of mature T cells is thought to help control the autoreactivity in peripheral T cells. The molecular basis for reduced sensitivity of peripheral T cells is not known. We found that peripheral T cells, but not immature thymocytes, lacking IFN-gamma-inducible lysosomal thiol reductase (GILT) display increased sensitivity to TCR ligation. GILT-/- peripheral T cells express reduced levels of mitochondrial superoxide dismutase 2 and consequently display higher levels of reactive oxygen radicals and ERK1/2 phosphorylation following activation. The increased sensitivity of GILT-deficient T cells results in a more severe hyperglycemia associated with streptozotocin-induced diabetes. GILT expression levels progressively increase in T cells with maturation. These data suggest that regulation of GILT expression may be a mechanism of T cell differentiation-associated changes in sensitivity to TCR engagement. |
