Chang C H, Guerder S, Hong S C, van Ewijk W, Flavell R A
Howard Hughes Medical Institute, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Immunity. 1996 Feb;4(2):167-78. doi: 10.1016/s1074-7613(00)80681-0.
CIITA activates the expression of multiple genes involved in antigen presentation and it is believed to be required for both constitutive and IFN gamma-inducible expression of these genes. To understand the role of CIITA in vivo, we have used gene targeting to generate mice that lack CIITA. CIITA-deficient (-/-) mice do not express conventional MHC class II molecules on the surface of splenic B cells and dendritic cells. In addition, macrophages resident in the peritoneal cavity do not express MHC class II molecules upon IFN gamma stimulation nor do somatic tissues of mice injected with IFN gamma, in contrast with wild-type mice. The levels of Ii and H-2M gene transcripts are substantially decreased but absent in CIITA (-/-) mice. The transcription of nonconventional MHC class II genes is, however not affected by CIITA deficiency. A subset of thymic epithelial cells express MHC class II molecules. Nonetheless, very few mature CD4 T cells are present in the periphery of CIITA (-/-) mice despite MHC class II expression in the thymus. Consequently, CIITA(-/-) mice are impaired in T-dependent antigen responses and MHC class II-mediated allogeneic responses.
CIITA可激活多个参与抗原呈递的基因的表达，并且被认为是这些基因组成型表达和IFNγ诱导型表达所必需的。为了了解CIITA在体内的作用，我们利用基因打靶技术培育出了缺乏CIITA的小鼠。CIITA缺陷型（-/-）小鼠的脾脏B细胞和树突状细胞表面不表达传统的MHC II类分子。此外，与野生型小鼠相比，腹腔内的巨噬细胞在受到IFNγ刺激时不表达MHC II类分子，注射了IFNγ的小鼠的体细胞组织也不表达。Ii和H-2M基因转录本的水平在CIITA（-/-）小鼠中大幅下降但不存在。然而，非传统MHC II类基因的转录不受CIITA缺陷的影响。一部分胸腺上皮细胞表达MHC II类分子。尽管如此，尽管胸腺中有MHC II类分子的表达，但CIITA（-/-）小鼠外周成熟CD4 T细胞却很少。因此，CIITA（-/-）小鼠的T细胞依赖性抗原反应和MHC II类介导的同种异体反应受损。
