Inability of IL-12 to Down-Regulate IgE Synthesis Due to Defective Production of IFN-γ in Atopic NC/Nga Mice1
Inability of IL-12 to Down-Regulate IgE Synthesis Due to Defective Production of IFN-γ in Atopic NC/Nga Mice1
复制标题
由于特应性 NC/Nga 小鼠中 IFN-γ 的产生缺陷，IL-12 无法下调 IgE 合成1
作者：
M. Matsumoto;A. Itakura;A. Tanaka;C. Fujisawa;H. Matsuda
在非无菌环境中饲养的NC/Nga小鼠自发患有特应性皮炎样皮肤病变，伴有IgE过度产生。我们研究了rIL-12对NC/Nga小鼠IgE产生的影响。rIL-12能有效地抑制OVA和氢氧化铝免疫BALB/c小鼠的IgE水平升高，但不能消除NC/Nga小鼠的IgE水平升高。rIL-12诱导的NC/Nga小鼠体内和体外IFN-γ的产生均低于BALB/c小鼠。在rIL-4和LPS中加入rIFN-γ可完全抑制BALB/c小鼠B细胞产生IgE，但不足以抑制NC/Nga小鼠B细胞产生IgE。在ConA预处理的脾细胞中，通过加入rIL-12，STAT 4在酪氨酸残基处被磷酸化，这在NC/Nga小鼠中比在BALB/c小鼠中更弱地诱导。最后，我们研究了rIL-12对NC/Nga小鼠特应性皮炎临床方面的预防能力。rIL-12给药导致在非无菌环境中饲养的NC/Nga小鼠的皮肤病变和IgE产生的恶化。这些结果表明，对IL-12不太敏感的T细胞产生IFN-γ的缺陷和B细胞对IFN-γ的低反应性可能有助于NC/Nga小鼠中IgE的过度产生，并且IL-12可能没有能力改善NC/Nga小鼠的临床方面。
NC/Nga mice raised in nonsterile circumstances spontaneously suffer from atopic dermatitis-like skin lesions with IgE hyperproduction. We investigated effects of rIL-12 on the IgE production in NC/Nga mice. rIL-12 administration was successful to suppress the increase of IgE levels in BALB/c mice immunized with OVA and aluminum hydroxide, but failed to abrogate that in NC/Nga mice. Both in vivo and in vitro IFN-γ production induced by rIL-12 was less in NC/Nga mice than in BALB/c mice. Addition of rIFN-γ to rIL-4 and LPS completely abrogated IgE production by B cells of BALB/c mice, but was insufficient to suppress it by B cells of NC/Nga mice. In splenic cells pretreated with Con A, STAT4 was phosphorylated at the tyrosine residue by addition of rIL-12, which was more weakly inducible in NC/Nga mice than in BALB/c mice. Finally, we examined the preventive ability of rIL-12 on the clinical aspects of atopic dermatitis in NC/Nga mice. rIL-12 administration resulted in exacerbation of development of the skin lesions and IgE production in NC/Nga mice raised in nonsterile circumstances. These results suggest that defective production of IFN-γ by T cells less sensitive to IL-12 and low responsiveness of B cells to IFN-γ may contribute to IgE hyperproduction in NC/Nga mice, and that IL-12 may have no ability to improve the clinical aspects of NC/Nga mice.
IL-12 通过影响共刺激分子 B7-1 (CD80) 和 B7-2 (CD86) 来逆转已建立的抗原特异性接触敏感性耐受性。
DOI：
--
发表时间：
1998
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ushio,H;Tsuji,RF;Szczepanik,M;Kawamoto,K;Matsuda,H;Askenase,PW
通讯作者：
Askenase,PW
特应性皮炎中 IL-10 的过度表达。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ohmen,JD;Hanifin,JM;Nickoloff,BJ;Rea,TH;Wyzykowski,R;Kim,J;Jullien,D;McHugh,T;Nassif,AS;Chan,SC
通讯作者：
Chan,SC
IL-4 和 IL-10 对特应性皮炎 IFN-γ 反应的下调作用。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lester,MR;Hofer,MF;Gately,M;Trumble,A;Leung,DY
通讯作者：
Leung,DY