title: A naive-like population of human CD1d-restricted T cells expressing intermediate levels of promyelocytic leukemia zinc finger.
abstract: Rare CD1d-α-galactosylceramide-specific T cells that do not express the invariant Vα24 chain of human NKT cells were recently identified after expansion in vitro with the lipid Ag, but their phenotype and frequency in vivo and lineage relationship with NKT cells could not be elucidated. By using a CD1d tetramer-based method to enrich these cells from fresh peripheral blood, we demonstrated their naive-like CD62L(high)CD45RO(-)CD4(+) phenotype and relatively high frequency of ∼10(-5) in several healthy individuals. Notably, these cells expressed the NKT lineage-specific transcription promyelocytic leukemia zinc finger (PLZF), indicating a developmental relationship with NKT cells and ruling out the possibility that they were conventional MHC-restricted T cells cross-reacting against CD1d-α-galactosylceramide. Although PLZF is known to direct the effector program of NKT cells, we show in this study that the naive-like cells expressed it at a significantly lower amount than NKT cells. Further, we present mouse studies demonstrating a sharp PLZF expression threshold requirement for induction of the effector phenotype. These findings directly demonstrate in vivo the existence of naive-like CD1d-restricted human T cells marked by intermediate levels of PLZF.
authors.affiliation: Committee on Immunology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Constantinides
authors.forename: Damien
authors.initials: D
authors.lastname: Picard
authors.forename: Adam K
authors.initials: AK
authors.lastname: Savage
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
mesh_terms: D000328:Adult; D000818:Animals; D055610:Antigens, CD1d / Q000097:blood / Q000502:physiology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000097:blood; D015473:Leukemia, Promyelocytic, Acute / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016192:Resting Phase, Cell Cycle / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D055815:Young Adult; D016335:Zinc Fingers
chemical_list: D055610:Antigens, CD1d; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C092037:ZBTB16 protein, human