A subset of NKT cells that lacks the NK1.1 marker, expresses CD1d molecules, and autopresents the alpha-galactosylceramide antigen.
In the present report, we characterize a novel T cell subset that shares with the NKT cell lineage both CD1d-restriction and high reactivity in vivo and in vitro to the alpha-galactosylceramide (alpha-GalCer) glycolipid. These cells preferentially use the canonical Valpha14-Jalpha281 TCR-alpha-chain and Vbeta8 TCR-beta segments, and are stimulated by alpha-GalCer in a CD1d-dependent fashion. However, in contrast to classical NKT cells, they lack the NK1.1 marker and express high surface levels of CD1d molecules. In addition, this NK1.1(-) CD1d(high) T subset, further referred to as CD1d(high) NKT cells, can be distinguished by its unique functional features. Although NK1.1(+) NKT cells require exogenous CD1d-presenting cells to make them responsive to alpha-GalCer, CD1d(high) NKT cells can engage their own surface CD1d in an autocrine and/or paracrine manner. Furthermore, in response to alpha-GalCer, CD1d(high) NKT cells produce high amounts of IL-4 and moderate amounts of IFN-gamma, a cytokine profile more consistent with a Th2-like phenotype rather than the Th0-like phenotype typical of NK1.1(+) NKT cells. Our work reveals a far greater level of complexity within the NKT cell population than previously recognized and provides the first evidence for T cells that can be activated upon TCR ligation by CD1d-restricted recognition of their ligand in the absence of conventional APCs.
Hameg
A
A
Institut National de La Santé et de la Recherche Médicale (INSERM) Unité 25 and Centre Claude Bernard, Hôpital Necker, Paris, France.
Apostolou
I
I
Leite-De-Moraes
M
M
Gombert
J M
JM
Garcia
C
C
Koezuka
Y
Y
Bach
J F
JF
Herbelin
A
A
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000941:Antigens / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D055610:Antigens, CD1d; D000950:Antigens, Ly; D000954:Antigens, Surface; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014176:Protein Biosynthesis; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000950:Antigens, Ly; D000954:Antigens, Surface; D015415:Biomarkers; D005699:Galactosylceramides; 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; D015847:Interleukin-4; D007371:Interferon-gamma