Journal
JOURNAL OF IMMUNOLOGY
Volume 187, Issue 3, Pages 1235-1242Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1100270
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- Academia Sinica [40-06]
- National Health Research Institute, Taiwan [NHRI-EX100-9943SI]
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The development of invariant NKT (iNKT) cells depends on the thymus. After positive selection by CD4+CD8+CD1d+ cortical thymocytes, iNKT cells proceed from CD44(low)NK1.1(-) (stage 1) to CD44(high)NK1.1(+) ( stage 2), and then to CD44(high)NK1.1(+) ( stage 3) cells. The programming of cytokine production occurs along the three differentiation stages, whereas the acquisition of NK receptors occurs at stage 3. Stage 3 thymic iNKT cells are specifically reduced in Il15ra(-/-) mice. The mechanism underlying this homeostatic deficiency and whether the IL-15 system affects other thymic iNKT cell developmental events remain elusive. In this study, we demonstrate that increased cell death contributed to the reduction of stage 3 cells in Il15ra(-/-) mice, as knockout of Bim restored this population. IL-15-dependent upregulation of Bcl-2 in stage 3 cells affected cell survival, as overexpression of hBcl-2 partially restored stage 3 cells in Il15ra(-/-) mice. Moreover, thymic iNKT cells in Il15ra(-/-) mice were impaired in functional maturation, including the acquisition of Ly49 and NKG2 receptors and the programming of cytokine production. Finally, IL15R alpha expressed by radiation-resistant cells is necessary and sufficient to support the survival as well as the examined maturation events of thymic iNKT cells. The Journal of Immunology, 2011, 187: 1235-1242.
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