| Autor: |
Jubala CM; University of Colorado Cancer Center, Aurora, CO, USA., Lamerato-Kozicki AR, Borakove M, Lang J, Gardner LA, Coffey D, Helm KM, Schaack J, Baier M, Cutter GR, Bellgrau D, Modiano JF |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2009 Feb; Vol. 58 (2), pp. 171-85. Date of Electronic Publication: 2008 Jun 04. |
| DOI: |
10.1007/s00262-008-0535-0 |
| Abstrakt: |
The survival of naive T cells is compromised in the absence of molecules encoded by the major histocompatibility complex (MHC) while antigen-experienced T cells survive. We hypothesized that survival pressures in an in vivo, MHC-deficient environment would permit enrichment of less frequent antigen-experienced autoreactive cells at the expense of the majority of antigen naive T cells. To test this hypothesis, we generated MHC class I- and class II-deficient mice in NOD and C57Bl/6 (B6) backgrounds, and examined the capacity of adoptively transferred autoimmune-prone NOD T cells, or non-autoimmune prone naive B6 T cells, respectively, to reject transplanted wild-type pancreatic islets or transplantable tumors in the MHC-deficient mice. In the MHC-deficient environment, CD4 T cells acquired self-hostile properties (islet rejection and tumor invasion) that were independent from their genetic propensity for autoreactivity, while CD8 T cells required appropriate prior exposure to antigen in order to survive and function (reject tumor) in this environment; however, disengagement of Tob1, a negative regulator of proliferation, led to a reverse phenotype with regard to persistence of CD4 and CD8 T cells in the MHC-deficient environment. Our data suggest that self-peptide/MHC interactions have dual roles to facilitate survival and restrain autoreactivity, thus acting as integral components of an intrinsic network of negative regulation that maintains tolerance. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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