NDLI: Development of innate CD4+ α-chain variable gene segment 24 (Vα24) natural killer T cells in the early human fetal thymus is regulated by IL-7

Content Provider	PubMed Central
Author	Sandberg, Johan K. Stoddart, Cheryl A. Brilot, Fabienne Jordan, Kimberly A. Nixon, Douglas F.
Copyright Year	2004
Abstract	Natural killer (NK) T cells are innate CD1d-restricted immune cells involved in regulation of immune tolerance, tumor immunity, and immunity to infectious pathogens. Human α-chain variable gene segment 24 (Vα24) NK T cells exist in the periphery as two functionally distinct subsets: one CD4+ and one CD4- subset. However, the developmental pathway of human Vα24 NK T cells is not well understood. Here, we show that Vα24 NK T cells develop in the fetal thymus. The relative number of intrathymic NK T cell precursors decline in a linear manner with gestational age, and they are very rare in the neonatal thymus, indicating that these cells preferentially develop in the early fetal thymus. Their restriction element, CD1d, is expressed by a vast majority of thymocytes. A majority of intrathymic Vα24 NK T cell progenitors are CD4+, whereas a minority are CD4/8+/+. CD4+ Vα24 NK T cell precursors show features of mature NK T cells, such as high levels of their semiinvariant T cell receptor and CD3 and some expression of CD161, whereas the CD4/8+/+ precursors seem less mature. The cytokine IL-7 shows a biphasic effect on Vα24 NK T cell progenitors in fetal thymic organ culture, with high doses driving proliferation of immature CD161-progenitors and low doses supporting survival and maturation. Thus, the data demonstrate that human Vα24 NK T cells of the CD4+, but not the CD4-, subset develop in the early fetal thymus. Furthermore, data suggest an intrathymic pathway of CD4+ Vα24 NK T cell development that is regulated by IL-7.
Related Links	http://dx.doi.org/10.1073/pnas.0305986101
Ending Page	7063
Page Count	6
Starting Page	7058
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	18
Volume Number	101
Language	English
Publisher	National Academy of Sciences
Publisher Date	2004-05-04
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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