Abstract
BackgroundInvariant natural killer T (iNKT) cells develop in the thymus and branch off from the maturation pathway of conventional T cell at the DP stage. While different stages of iNKT cellular development have been defined, the actual time that iNKT cell precursors spend at each stage is still unknown.Methodology/Principal FindingHere we report on maturation dynamics of post-selection DN iNKT cells by injecting wild-type DPdim thymocytes into the thymus of TCRα−/− mice and using the Vα14-Jα18 rearrangements as a molecular marker to follow the maturation dynamics of these cells.Conclusion/SignificanceThis study shows that the developmental dynamics of DN iNKT cells in DPdim are very rapid and that it takes less than 1 day to down-regulate CD4 and CD8 and become DN. These DN cells are precursors of peripheral DN iNKT cells and appear in the spleen in 1–2 days. Thymic DN iNKT residents are predominantly derived from cells that quickly return from the periphery. The expansion of a very small subset of DN iNKT precursors could also play a small role in this process. These data are an example of measuring T cell maturation in the thymus and show that the maturation dynamics of selected DN iNKT cells fall within the same general time frame as conventional αβ T cells.
Highlights
T cells are divided into several subsets based on the expression of their antigen receptor and their function
In this study we used rearrangement analysis together with intrathymic transfer of wild-type DPdim to TCRa 2/2 mice to describe the dynamics of DN Invariant natural killer T (iNKT) maturation in the absence of continuing input from the bone marrow
Since we had previously shown that rearrangement studies are sensitive techniques for studying thymocyte development [21,22], we took advantage of the unique Va14-Ja18 rearrangement and used it as a molecular marker for tracking the maturation of iNKT cells
Summary
T cells are divided into several subsets based on the expression of their antigen receptor and their function. T cells expressing the ab T cell receptor (TCR) constitute the majority of peripheral T cells, and they generally respond to peptides presented by MHC class I or class II molecules. A small subset of ab T cells respond to lipids presented by a non-classical MHC molecule, CD1d. Because they express surface markers normally associated with NK cells, they are referred to as NKT cells. Different stages of development are defined by the expression of T cell receptor (TCR), its co-receptors, CD4 and CD8, and other accessory molecules. Selection of the cells that have in-frame rearrangement is referred to as b selection This selection takes place in cells that do not yet express CD4 and/or CD8 co-receptors (CD42CD82 double-negative cells, DN). While different stages of iNKT cellular development have been defined, the actual time that iNKT cell precursors spend at each stage is still unknown
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