Thymus-independent generation of NK1+ T cells in vitro from fetal liver precursors.
NK1.1+TCR alpha beta+ (NK1+) T cells are an unusual subset of mouse TCR alpha beta+ cells found primarily in adult thymus and liver. In contrast to conventional TCR alpha beta+ cells, NK1+ T cells have a TCR repertoire that is highly skewed to V alpha14 and to Vbeta8, -7, and -2. The developmental origin and ligand specificity of NK1+ T cells are controversial. We show here that NK1+ T cells with a typically biased V alpha and V beta repertoire develop in cytokine-supplemented suspension cultures of fetal liver established from either normal or athymic mice. Furthermore, NK1+ T cell development in fetal liver cultures is abrogated in beta2m-deficient mice (which lack MHC class I and other related molecules) and can be partially inhibited by the presence of anti-CD1 mAbs. Moreover, mixing experiments indicate that recombination-deficient SCID fetal liver cells can reconstitute NK1+ T cell development in beta2m-deficient fetal liver cultures. Collectively, our data demonstrate that NK1+ T cells can develop extrathymically from fetal liver precursors and that a beta2m-associated ligand (putatively CD1) present on nonlymphoid cells is essential for their positive selection and/or expansion.
Shimamura
M
M
Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
Ohteki
T
T
Launois
P
P
Garcia
A M
AM
MacDonald
H R
HR
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D018949:Antigens, CD1; D016693:Receptors, Antigen, T-Cell, alpha-beta