Targeted expression of human CD1d in transgenic mice reveals independent roles for thymocytes and thymic APCs in positive and negative selection of Vα14i NKT cells

Jens Schümann, Paola Pittoni, Elena Tonti, H. Robson MacDonald, Paolo Dellabona, Giulia Casorati

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Abstract

CD1d-dependent invariant Vα14 (Vα14i) NKT cells are innate T lymphocytes expressing a conserved semi-invariant TCR, consisting, in mice, of the invariant Vα14-Jα18 TCR α-chain paired mostly with Vβ8.2 and Vα7. The cellular requirements for thymic positive and negative selection of Vα14i NKT cells are only partially understood. Therefore, we generated transgenic mice expressing human CD1d (hCD1d) either on thymocytes, mainly CD4+ CD8+ double positive, or on APCs, the cells implicated in the selection of Vα14i NKT cells. In the absence of the endogenous mouse CD1d (mCD1d), the expression of hCD1d on thymocytes, but not on APCs, was sufficient to select Vα14i NKT cells that proved functional when activated ex vivo with the Ag α-galactosyl ceramide. Vα14i NKT cells selected by hCD1d on thymocytes, however, attained lower numbers than in control mice and expressed essentially Vβ8.2. The low number of Vβ8.2+ Vα14i NKT cells selected by hCD1d on thymocytes was not reversed by the concomitant expression of mCD1d, which, instead, restored the development of Vβ7+ Vα14i NKT cells. Vβ8.2+, but not Vβ7+, NKT cell development was impaired in mice expressing both hCD1d on APCs and mCD1d. Taken together, our data reveal that selective CD1d expression by thymocytes is sufficient for positive selection of functional Vα14i NKT cells and that both thymocytes and APCs may independently mediate negative selection.

Original languageEnglish
Pages (from-to)7303-7310
Number of pages8
JournalJournal of Immunology
Volume175
Issue number11
Publication statusPublished - Dec 1 2005

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Natural Killer T-Cells
Thymocytes
Transgenic Mice
Galactosylceramides
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

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Targeted expression of human CD1d in transgenic mice reveals independent roles for thymocytes and thymic APCs in positive and negative selection of Vα14i NKT cells. / Schümann, Jens; Pittoni, Paola; Tonti, Elena; MacDonald, H. Robson; Dellabona, Paolo; Casorati, Giulia.

In: Journal of Immunology, Vol. 175, No. 11, 01.12.2005, p. 7303-7310.

Research output: Contribution to journalArticle

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