| First Author | Bezbradica JS | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 14 | Pages | 5114-9 |
| PubMed ID | 15792999 | Mgi Jnum | J:97416 |
| Mgi Id | MGI:3575388 | Doi | 10.1073/pnas.0408449102 |
| Citation | Bezbradica JS, et al. (2005) Commitment toward the natural T (iNKT) cell lineage occurs at the CD4+8+ stage of thymic ontogeny. Proc Natl Acad Sci U S A 102(14):5114-9 |
| abstractText | 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), Valpha14Jalpha18 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 Valpha14Jalpha18-positive iNKT cells that are CD4(+)8(+). In resolution to this issue, we demonstrate that retinoic acid receptor-related orphan receptor gamma (RORgamma)(0/0) thymi, which accumulate immature single-positive (ISP) thymocytes that precede the DP stage, do not rearrange Valpha14-to-Jalpha18 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 RORgamma(0/0) mice, which promotes survival and permits secondary rearrangements of distal Valpha and Jalpha gene segments at the DP stage, rescues Valpha14-to-Jalpha18 recombination. Similarly, introgression of a rearranged Valpha14Jalpha18 transgene into RORgamma(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 Valpha14-to-Jalpha18 rearrangement, positive selection, and iNKT cell lineage commitment occur at or after the DP stage of ontogeny. |
