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PMID: 11877485 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining.

The Journal of experimental medicine ·Vol. 195 ·No. 5 ·2002-03-04 ·Pages 625-36

Gumperz JE, Miyake S, Yamamura T, Brenner MB

Abstract

CD1d-restricted natural killer (NK)T cells are known to potently secrete T helper (Th)1 and Th2 cytokines and to mediate cytolysis, but it is unclear how these contrasting functional activities are regulated. Using lipid antigen-loaded CD1d tetramers, we have distinguished two subsets of CD1d-restricted T cells in fresh peripheral blood that differ in cytokine production and cytotoxic activation. One subset, which was CD4(-), selectively produced the Th1 cytokines interferon gamma and tumor necrosis factor alpha, and expressed NKG2d, a marker associated with cytolysis of microbially infected and neoplastic cells. This subset up-regulated perforin after exposure to interleukin (IL)-2 or IL-12. In contrast, CD4(+) CD1d-restricted NKT cells potently produced both Th1 and Th2 cytokines, up-regulated perforin in response to stimulation by phorbol myristate acetate and ionomycin but not IL-2 or IL-12, and could be induced to express CD95L. Further, for both CD1d-restricted NKT cell subsets, we found that antigenic stimulation induced cytokine production but not perforin expression, whereas exposure to inflammatory factors enhanced perforin expression but did not stimulate cytokine production. These results show that the various activities of CD1d-restricted T cells in tumor rejection, autoimmune disease, and microbial infections could result from activation of functionally distinct subsets, and that inflammatory and antigenic stimuli may influence different effector functions.

MeSH Terms
Animals Antigens, CD1/chemistry,physiology Antigens, CD1d Antigens, Surface/analysis Cytokines/biosynthesis Cytotoxicity, Immunologic Galactosylceramides/pharmacology Humans Killer Cells, Natural/immunology Lectins, C-Type Mice NK Cell Lectin-Like Receptor Subfamily B NK Cell Lectin-Like Receptor Subfamily K Receptors, Immunologic/analysis Receptors, Lymphocyte Homing/analysis Receptors, Natural Killer Cell Staining and Labeling
Chemicals
Antigens, CD1 Antigens, CD1d Antigens, Surface CD1D protein, human Cytokines Galactosylceramides KLRB1 protein, human KLRK1 protein, human Klrk1 protein, mouse Lectins, C-Type NK Cell Lectin-Like Receptor Subfamily B NK Cell Lectin-Like Receptor Subfamily K Receptors, Immunologic Receptors, Lymphocyte Homing Receptors, Natural Killer Cell
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gumperz Jenny E
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, One Jimmy Fund Way, Boston, MA 02115, USA.
Miyake Sachiko
Yamamura Takashi
Brenner Michael B
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20011786
Published
2002-03-04
Pages
625-36
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193772
Subset
IM
Grants
NIAID NIH HHS · T32 AI007306 · United States
NIAID NIH HHS · R37 AI028973 · United States
NIAID NIH HHS · T32-AI07306 · United States
NIAID NIH HHS · AI28973 · United States
NIAID NIH HHS · R01 AI028973 · United States
External Links
PubMed source DOI: 10.1084/jem.20011786 PMC Full Text View journal details
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