TY - JOUR
T1 - Down-regulation of the invariant Vα14 antigen receptor in NKT cells upon activation
AU - Harada, Michishige
AU - Seino, Ken Ichiro
AU - Wakao, Hiroshi
AU - Sakata, Sakura
AU - Ishizuka, Yuko
AU - Ito, Toshihiro
AU - Kojo, Satoshi
AU - Nakayama, Toshinori
AU - Taniguchi, Masaru
N1 - Funding Information:
The authors thank Ms Hiroko Tanabe for the preparation of this manuscript and Kirin Brewery Co. Ltd for support of this study. This work was in part supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (Japan) through a grant under the Special Coordination Fund for the Promotion of Science and Technology (T. N.), and through Grants-in-Aid for Scientific Research C#13218016 (T. N.), A#13307011 (M. T.), B#14370107 (T. N.) and C#12670293 (T. N.); the Program for the Promotion of Fundamental Studies in Health Sciences, Organization for Pharmaceutical Safety and Research, Ministry of Health, Labor and Welfare (M. T.); and the Human Frontier Science Program, RG00168/2000-M206 (M. T).
PY - 2004/2
Y1 - 2004/2
N2 - NKT cells expressing the invariant Vα14 antigen receptor constitute a novel lymphocyte subpopulation with immunoregulatory functions. Stimulation via their invariant Vα14 receptor with anti-CD3 or a ligand, α-galactosylceramide (α-GalCer), triggers activation of Vα14 NKT cells, resulting in a rapid cytokine production such as IFN-γ and IL-4. Soon after their receptor activation, Vα14 NKT cells disappeared as judged by staining with CD1d tetramer loaded with (α-GalCer (α-GalCer/CD1d tetramer), which has been believed to be due to apoptotic cell death. Here we show that such a disappearance was largely attributed to down-regulation of the Vα14 receptor. In fact, Vα14 NKT cells were relatively resistant to apoptosis compared to the conventional T cells as evidenced by less staining with Annexin-V, a limited DNA fragmentation, and their preferential expression of anti-apoptotic genes such as NAIP and MyD118. Furthermore, they did not become tolerant, and maintained their proliferative capacity and cytokine production even after their receptor down-regulation. These as yet unrecognized facets of Vα14 NKT cells are discussed in relation to their regulatory functions.
AB - NKT cells expressing the invariant Vα14 antigen receptor constitute a novel lymphocyte subpopulation with immunoregulatory functions. Stimulation via their invariant Vα14 receptor with anti-CD3 or a ligand, α-galactosylceramide (α-GalCer), triggers activation of Vα14 NKT cells, resulting in a rapid cytokine production such as IFN-γ and IL-4. Soon after their receptor activation, Vα14 NKT cells disappeared as judged by staining with CD1d tetramer loaded with (α-GalCer (α-GalCer/CD1d tetramer), which has been believed to be due to apoptotic cell death. Here we show that such a disappearance was largely attributed to down-regulation of the Vα14 receptor. In fact, Vα14 NKT cells were relatively resistant to apoptosis compared to the conventional T cells as evidenced by less staining with Annexin-V, a limited DNA fragmentation, and their preferential expression of anti-apoptotic genes such as NAIP and MyD118. Furthermore, they did not become tolerant, and maintained their proliferative capacity and cytokine production even after their receptor down-regulation. These as yet unrecognized facets of Vα14 NKT cells are discussed in relation to their regulatory functions.
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U2 - 10.1093/intimm/dxh023
DO - 10.1093/intimm/dxh023
M3 - Article
C2 - 14734609
AN - SCOPUS:1042280962
SN - 0953-8178
VL - 16
SP - 241
EP - 247
JO - International Immunology
JF - International Immunology
IS - 2
ER -