Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells.
NKT cells, defined as T cells expressing the NK cell marker NK1.1, are involved in tumor rejection and regulation of autoimmunity via the production of cytokines. We show in this study that two types of NKT cells can be defined on the basis of their reactivity to the monomorphic MHC class I-like molecule CD1d. One type of NKT cell is positively selected by CD1d and expresses a biased TCR repertoire together with a phenotype found on activated T cells. A second type of NKT cell, in contrast, develops in the absence of CD1d, and expresses a diverse TCR repertoire and a phenotype found on naive T cells and NK cells. Importantly, the two types of NKT cells segregate in distinct tissues. Whereas thymus and liver contain primarily CD1d-dependent NKT cells, spleen and bone marrow are enriched in CD1d-independent NKT cells. Collectively, our data suggest that recognition of tissue-specific ligands by the TCR controls localization and activation of NKT cells.
Eberl
G
G
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
Lees
R
R
Smiley
S T
ST
Taniguchi
M
M
Grusby
M J
MJ
MacDonald
H R
HR
D000818:Animals; D000941:Antigens / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000502:physiology*; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D000950:Antigens, Ly; D000954:Antigens, Surface; D015415:Biomarkers; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D005260:Female; D019673:Genes, T-Cell Receptor alpha / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009928:Organ Specificity / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C045084:invariant chain