Commitment toward the natural T (iNKT) cell lineage occurs at the CD4 +8+ stage of thymic ontogeny

Bezbradica J.S., Hill T., Stanic A.K., Van Kaer L. and Joyce S. (2005) Commitment toward the natural T (iNKT) cell lineage occurs at the CD4 +8+ stage of thymic ontogeny. Proceedings of the National Academy of Sciences of the United States of America, 102 14: 5114-5119. doi:10.1073/pnas.0408449102


Author Bezbradica J.S.
Hill T.
Stanic A.K.
Van Kaer L.
Joyce S.
Title Commitment toward the natural T (iNKT) cell lineage occurs at the CD4 +8+ stage of thymic ontogeny
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
Publication date 2005-04-05
Sub-type Article (original research)
DOI 10.1073/pnas.0408449102
Volume 102
Issue 14
Start page 5114
End page 5119
Total pages 6
Language eng
Subject 1311 Genetics
1000 General
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), Vα14Jα18 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 Vα14Jα18-positive iNKT cells that are CD4+8+. In resolution to this issue, we demonstrate that retinoic acid receptor-related orphan receptor γ (RORγ)0/0 thymi, which accumulate immature single-positive (ISP) thymocytes that precede the DP stage, do not rearrange Vα14-to-Jα18 gene segments, suggesting that this event occurs at a post-ISP stage. Mixed radiation bone marrow chimeras revealed that RORγ functions in an iNKT cell lineage-specific manner. Further, introgression of a Bcl-xL transgene into RORγ0/0 mice, which promotes survival and permits secondary rearrangements of distal Vα and Jα gene segments at the DP stage, rescues Vα14-to-Jα18 recombination. Similarly, introgression of a rearranged Vα14Jα18 transgene into RORγ0/0 mice results in functional iNKT cells. Thus, our data support the "T cell receptor-instructive (mainstream precursor) model" of iNKT cell lineage specification where Vα14-to-Jα18 rearrangement, positive selection, and iNKT cell lineage commitment occur at or after the DP stage of ontogeny.
Keyword Lineage specification
RORγ
T cell ontogeny
Vα14-to-Jα18 rearrangement
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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