Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction.
Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction.
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可溶性 HLA I 类在通过 FasL-Fas 相互作用与杀伤细胞激活 HLA I 类受体结合后诱导 NK 细胞凋亡。
作者：
G. Spaggiari;P. Contini;A. Dondero;R. Carosio;F. Puppo;F. Indiveri;M. Zocchi;A. Poggi
C型凝集素抑制性受体（CLIR）或杀伤性Ig样受体（KIR）的激活亚型与其天然配体（以可溶性HLA-I（sHLA-I）分子为代表）的结合可诱导自然杀伤（NK）细胞的程序性细胞死亡。事实上，无论是假定的HLA-E或HLA-F诱导的NK细胞凋亡，（sHLA-I非-A、-B、-C和-G）或sHLA-I-Cw 4或-Cw 3，分别来自未转染或-Cw 4或-Cw 3等位基因转染的HLA-A（-）、B（-）、C（-）、G（-）、E（+）、F（+）721.221淋巴母细胞样细胞系，通过用抗CLIR或抗KIR特异性单克隆抗体（mAb）覆盖相应的活化受体来阻断。NK细胞与sHLA-Ⅰ型激活受体相互作用后，产生并释放Fas配体（FasL），通过与NK细胞表面Fas相互作用导致NK细胞凋亡。阻断抗Fas mAb或抗FasL mAb可通过激活NK细胞克隆中的受体抑制sHLA-I介导的凋亡。这种细胞凋亡被抑制的NK细胞治疗与环孢素A，而这种药物对激活受体介导的活化细胞溶解没有影响。相反，康卡霉素A，一种颗粒的空泡型H（+）-腺苷三磷酸酶（H（+）-ATP酶）的抑制剂，抑制活化受体诱导的NK细胞溶解，表明活化受体介导的细胞凋亡和细胞溶解可以使用不同的细胞内途径。此外，在与适当的sHLA-I配体孵育的活化受体（+）NK细胞的培养上清液中可检测到大量的干扰素-γ（IFN-γ）。同样，环孢菌素A，而不是康卡霉素A，强烈减少激活受体介导的IFN-γ的产生。这表明激活受体诱导的NK细胞凋亡可以在消除潜在有害的NK细胞克隆中发挥作用，同时，它导致IFN-γ的产生，IFN-γ是一种能够放大免疫应答的抗病毒细胞因子。
The engagement of the activating isoforms of C-type lectin inhibitory receptor (CLIR) or killer Ig-like receptor (KIR) by their natural ligands, represented by soluble HLA-I (sHLA-I) molecules, induced programmed cell death of natural killer (NK) cells. Indeed, NK cell apoptosis elicited by either putative HLA-E and HLA-F (sHLA-I non-A, -B, -C, and -G) or sHLA-I-Cw4 or -Cw3 from untransfected or -Cw4 or -Cw3 alleles transfected HLA-A(-), B(-), C(-), G(-), E(+), F(+) 721.221 lymphoblastoid cell line, respectively, was blocked by covering the corresponding activating receptor with either anti-CLIR- or anti-KIR-specific monoclonal antibodies (mAbs). After sHLA-I-activating receptor interaction, NK cells produced and released Fas ligand (FasL), which in turn led to NK cell apoptosis by interacting with Fas at the NK cell surface. Blocking anti-Fas mAb, or anti-FasL mAb, inhibited sHLA-I-mediated apoptosis via activating receptor in NK cell clones. This apoptosis was inhibited by NK cell treatment with cyclosporin A, whereas this drug had no effect on activating receptor-mediated activation of cytolysis. Conversely, concanamycin A, an inhibitor of vacuolar type H(+)-adenosine triphosphatase (H(+)-ATPase) of granules, inhibited activating receptor-induced NK cell cytolysis, suggesting that activating receptor-mediated apoptosis and cytolysis can use different intracellular pathways. Furthermore, a large amount of interferon-gamma (IFN-gamma) was detectable in culture supernatant of activating receptor(+) NK cells incubated with the appropriate sHLA-I ligand. Again, cyclosporin A, but not concanamycin A, strongly reduced activating receptor-mediated IFN-gamma production. This suggests that activating receptor-induced apoptosis of NK cells could play a role in eliminating potentially harmful NK cell clones and, at the same time, it leads to production of IFN-gamma, an antiviral cytokine able to amplify immune responses.
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NK 细胞相关 Fas 配体在细胞介导的细胞毒性和细胞凋亡中的作用。
DOI：
10.1016/s0923-2494(97)84219-8
发表时间：
1997
期刊：
Research in immunology
影响因子：
--
作者：
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通讯作者：
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DOI：
10.1016/0167-5699(95)80127-8
发表时间：
1995-03
期刊：
Immunology today
影响因子：
--
作者：
F. Puppo;M. Scudeletti;F. Indiveri;S. Ferrone
通讯作者：
F. Puppo;M. Scudeletti;F. Indiveri;S. Ferrone
配体与 Fc gamma R 结合可诱导 IL-2 刺激的 NK 细胞发生 c-myc 依赖性细胞凋亡。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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通讯作者：
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影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
影响因子：
4.4
作者：
N. Lee;D. Goodlett;A. Ishitani;H. Marquardt;D. Geraghty
通讯作者：
N. Lee;D. Goodlett;A. Ishitani;H. Marquardt;D. Geraghty