Dissociated expression of natural killer 1.1 and T-cell receptor by invariant natural killer T cells after interleukin-12 receptor and T-cell receptor signalling.
Invariant (i) natural killer T (NKT) cells become undetectable after stimulation with alpha-galactosylceramide (alpha-GalCer) or interleukin (IL)-12. Although down-modulation of surface T-cell receptor (TCR)/NKR-P1C (NK1.1) expression has been shown convincingly after stimulation with alpha-GalCer, it is unclear whether this also holds true for IL-12 stimulation. To determine whether failure to detect iNKT cells after IL-12 stimulation is caused by dissociation/internalization of TCR and/or NKR-P1C, or by block of de novo synthesis of these molecules, and to examine the role of IL-12 in the disappearance of iNKT cells after stimulation with alpha-GalCer, surface (s)/cytoplasmic (c) protein expression, as well as messenger RNA (mRNA) expression of TCR/NKR-P1C by iNKT cells after stimulation with alpha-GalCer or IL-12, and the influence of IL-12 neutralization on the down-modulation of sTCR/sNKR-P1C expression by iNKT cells after stimulation with alpha-GalCer were examined. The s/cTCR(+ )s/cNKR-P1C(+) iNKT cells became undetectable after in vivo administration of alpha-GalCer, which was partially prevented by IL-12 neutralization. Whereas s/cNKR-P1C(+) iNKT cells became undetectable after in vivo administration of IL-12, s/cTCR(+) iNKT cells were only marginally affected. mRNA expression of TCR/NKR-P1C remained unaffected by alpha-GalCer or IL-12 treatment, despite the down-modulation of cTCR and/or cNKR-P1C protein expression. By contrast, cTCR(+ )cNKR-P1C(+) sTCR(-) sNKR-P1C(-) iNKT cells and cNKR-P1C(+) sNKR-P1C(-) iNKT cells were detectable after in vitro stimulation with alpha-GalCer and IL-12, respectively. Our results indicate that TCR and NKR-P1C expression by iNKT cells is differentially regulated by signalling through TCR and IL-12R. They also suggest that IL-12 participates, in part, in the disappearance of iNKT cells after stimulation with alpha-GalCer by down-modulating not only sNKR-P1C, but also sTCR.
Emoto
Masashi
M
Laboratory of Immunology, Department of Laboratory Sciences, Gunma University School of Health Sciences, Maebashi, Gunma, Japan. memoto@health.gunma-u.ac.jp
Shimizu
Takamitsu
T
Koike
Hiromi
H
Yoshizawa
Izumi
I
Hurwitz
Robert
R
Kaufmann
Stefan H E
SH
Emoto
Yoshiko
Y
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000950:Antigens, Ly / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D019138:Antibodies, Blocking; D000950:Antigens, Ly; D005699:Galactosylceramides; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011948:Receptors, Antigen, T-Cell; C493154:alpha-galactosylceramide; D018664:Interleukin-12