Down-regulation of the invariant Valpha14 antigen receptor in NKT cells upon activation.
NKT cells expressing the invariant Valpha14 antigen receptor constitute a novel lymphocyte subpopulation with immunoregulatory functions. Stimulation via their invariant Valpha14 receptor with anti-CD3 or a ligand, alpha-galactosylceramide (alpha-GalCer), triggers activation of Valpha14 NKT cells, resulting in a rapid cytokine production such as IFN-gamma and IL-4. Soon after their receptor activation, Valpha14 NKT cells disappeared as judged by staining with CD1d tetramer loaded with alpha-GalCer (alpha-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 Valpha14 receptor. In fact, Valpha14 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 Valpha14 NKT cells are discussed in relation to their regulatory functions.
Harada
Michishige
M
RIKEN Research Center for Allergy and Immunology, Graduate School of Medicine, Chiba University, Chiba City, Chiba 260-8670, Japan.
Seino
Ken-Ichiro
K
Wakao
Hiroshi
H
Sakata
Sakura
S
Ishizuka
Yuko
Y
Ito
Toshihiro
T
Kojo
Satoshi
S
Nakayama
Toshinori
T
Taniguchi
Masaru
M
D000818:Animals; D017302:Annexins / Q000378:metabolism; D000943:Antigens, Differentiation / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D017252:CD3 Complex / Q000276:immunology* / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D005699:Galactosylceramides / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D051616:Neuronal Apoptosis-Inhibitory Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D000097642:GADD45 Proteins
D017302:Annexins; D000943:Antigens, Differentiation; D017252:CD3 Complex; D005699:Galactosylceramides; D007371:Interferon-gamma; D015847:Interleukin-4; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C496801:Naip1 protein, mouse