Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc

被引:254
作者
Ranger, AM
Hodge, MR
Gravallese, EM
Oukka, M
Davidson, L
Alt, FW
de la Brousse, FC
Hoey, T
Grusby, M
Glimcher, LH
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA
[2] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA
[3] Tularik Inc, San Francisco, CA 94080 USA
关键词
D O I
10.1016/S1074-7613(00)80465-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The NF-AT family of transcription factors activates early immune response genes such as cytokines. In the adult, NF-ATc is expressed exclusively in the lymphoid system and is induced upon lymphocyte activation. NF-ATc null mutant mice die in utero of cardiac failure, precluding analysis of the role of NF-ATc in lymphocyte activation. By using BAG-e-deficient blastocyst complementation, we now demonstrate that young, highly chimeric mice lacking NF-ATc have impaired repopulation of both thymus and peripheral lymphoid organs. Furthermore, NF-ATc deficiency impaired T lymphocyte activation and secretion of IL-4. B lymphocytes displayed reduced proliferation and a selective loss of IL-4-driven immunoglobulin isotypes both in vivo and in vitro. Our data demonstrate that NF-ATc is essential for the optimal generation and function of mature T and B lineage cells, with an especially profound effect on IL-4-driven responses.
引用
收藏
页码:125 / 134
页数:10
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