| First Author | Bruce D | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 5 | Pages | 2819-25 |
| PubMed ID | 21270396 | Mgi Jnum | J:169395 |
| Mgi Id | MGI:4940927 | Doi | 10.4049/jimmunol.1003444 |
| Citation | Bruce D, et al. (2011) Intrinsic Requirement for the Vitamin D Receptor in the Development of CD8{alpha}{alpha}-Expressing T Cells. J Immunol 186(5):2819-25 |
| abstractText | Vitamin D and vitamin D receptor (VDR) deficiency results in severe symptoms of experimental inflammatory bowel disease in several different models. The intraepithelial lymphocytes of the small intestine contain large numbers of CD8alphaalpha(+) T cells that have been shown to suppress the immune response to Ags found there. In this study, we determined the role of the VDR in the development of CD8alphaalpha(+) T cells. There are fewer total numbers of TCRalphabeta(+) T cells in the gut of VDR knockout (KO) mice, and that reduction was largely in the CD8alphaalpha(+) TCRalphabeta(+) cells. Conversely TCRgammadelta(+) T cells were normal in the VDR KO mice. The thymic precursors of CD8alphaalpha(+) TCRalphabeta(+) cells (triple-positive for CD4, CD8alphaalpha, and CD8alphabeta) were reduced and less mature in VDR KO mice. In addition, VDR KO mice had a higher frequency of the CD8alphaalpha(+) TCRalphabeta(+) precursors (double-negative [DN] TCRalphabeta(+) T cells) in the gut. The proliferation rates of the DN TCRalphabeta(+) gut T cells were less in the VDR KO compared with those in wild type. Low proliferation of DN TCRalphabeta(+) T cells was a result of the very low expression of the IL-15R in this population of cells in the absence of the VDR. Bone marrow transplantation showed that the defect in VDR KO CD8alphaalpha(+) TCRalphabeta(+) cells was cell intrinsic. Decreased maturation and proliferation of CD8alphaalpha(+) TCRalphabeta(+) cells in VDR KO mice results in fewer functional CD8alphaalpha(+) TCRalphabeta(+) T cells, which likely explains the increased inflammation in the gastrointestinal tract of VDR KO and vitamin D-deficient mice. |
