التفاصيل البيبلوغرافية
| العنوان: |
Invariant Natural Killer T-Cell Control of Type 1 Diabetes: A Dendritic Cell Genetic Decision of a Silver Bullet or Russian Roulette. |
| المؤلفون: |
Driver, John P., Scheuplein, Felix, Chen, Yi-Guang, Grier S., Alexandra E., Wilson, Brian, Serreze, David V. |
| المصدر: |
Diabetes; Feb2010, Vol. 59 Issue 2, p423-432, 10p, 7 Graphs |
| مصطلحات موضوعية: |
KILLER cells, T cells, AUTOIMMUNE diseases, DENDRITIC cells, ANTIGEN-antibody reactions, GENETICS of diabetes |
| مستخلص: |
OBJECTIVE--In part, activation of invariant natural killer T (iNKT)-cells with the superagonist α-galactosylceramide (α-GalCer) inhibits the development of T-cell-mediated autoimmune type 1 diabetes in NOD mice by inducing the downstream differentiation of antigen-presenting dendritic cells (DCs) to an immunotolerogenic state. However, in other systems iNKT-cell activation has an adjuvant-like effect that enhances rather than suppresses various immunological responses. Thus, we tested whether in some circumstances genetic variation would enable activated iNKT-cells to support rather than inhibit type 1 diabetes development. RESEARCH DESIGN AND METHODS--We tested whether iNKT-conditioned DCs in NOD mice and a major histocompatibility complex-matched C57BL/6 (B6) background congenic stock differed in capacity to inhibit type 1 diabetes induced by the adoptive transfer of pathogenic AI4 CD8 T-cells. RESULTS--Unlike those of NOD origin, iNKT-conditioned DCs in the B6 background stock matured to a state that actually supported rather than inhibited AI4 T-cell-induced type 1 diabetes. The induction of a differing activity pattern of T-cell costimulatory molecules varying in capacity to override programmed death-ligand-1 inhibitory effects contributes to the respective ability of iNKT-conditioned DCs in NOD and B6 background mice to inhibit or support type 1 diabetes development. Genetic differences inherent to both iNKT-cells and DCs contribute to their varying interactions in NOD and B6.H2[sup g7] mice. CONCLUSIONS--This great variability in the interactions between iNKT-cells and DCs in two inbred mouse strains should raise a cautionary note about considering manipulation of this axis as a potential type 1 diabetes prevention therapy in genetically heterogeneous humans. Diabetes 59:423-432, 2010 [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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