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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Van Kaer, Luc Joyce, Sebastian Hill, Timothy Bezbradica, Jelena S. Stanic, Aleksandar K. |
| Description | Author Affiliation: Bezbradica JS ( Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.); |
| Abstract | T lineage commitment occurs in a discrete, stage-specific manner during thymic ontogeny. Intrathymic precursor transfer experiments and the identification of CD4(+)8+ double-positive (DP), V alpha 14J alpha 18 natural T (iNKT) cells suggest that commitment to this lineage might occur at the DP stage. Nevertheless, this matter remains contentious because others failed to detect V alpha 14J alpha 18-positive iNKT cells that are CD4(+)8+. In resolution to this issue, we demonstrate that retinoic acid receptor-related orphan receptor gamma (ROR gamma)0/0 thymi, which accumulate immature single-positive (ISP) thymocytes that precede the DP stage, do not rearrange V alpha 14-to-J alpha 18 gene segments, suggesting that this event occurs at a post-ISP stage. Mixed radiation bone marrow chimeras revealed that RORgamma functions in an iNKT cell lineage-specific manner. Further, introgression of a Bcl-x(L) transgene into ROR gamma(0/0) mice, which promotes survival and permits secondary rearrangements of distal V alpha and J alpha gene segments at the DP stage, rescues V alpha 14-to-J alpha 18 recombination. Similarly, introgression of a rearranged V alpha 14J alpha 18 transgene into ROR gamma(0/0) mice results in functional iNKT cells. Thus, our data support the 'T cell receptor-instructive (mainstream precursor) model' of iNKT cell lineage specification where V alpha 14-to-J alpha 18 rearrangement, positive selection, and iNKT cell lineage commitment occur at or after the DP stage of ontogeny. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 14 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Killer Cells, Natural Cytology Immunology T-Lymphocyte Subsets Animals CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Cell Differentiation DNA, Complementary Genetics Gene Rearrangement, T-Lymphocyte Immunity, Innate Lymphopoiesis Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Models, Immunological Nuclear Receptor Subfamily 1, Group F, Member 3 Radiation Chimera Receptors, Retinoic Acid Deficiency Receptors, Thyroid Hormone Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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