An interleukin 4 (IL-4)-independent pathway for CD4(+) T cell IL-4 production is revealed in IL-4 receptor-deficient mice
An interleukin 4 (IL-4)-independent pathway for CD4(+) T cell IL-4 production is revealed in IL-4 receptor-deficient mice
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DOI：
10.1073/pnas.94.20.10838
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发表时间：
1997-09-30
影响因子：
11.1
通讯作者：
Paul, WE
中科院分区：
文献类型：
--
作者：
NobenTrauth, N;Shultz, LD;Paul, WE
用BALB/c胚胎干细胞进行基因打靶，获得IL-4受体α链(IL-4Rα)缺陷小鼠。突变小鼠表现出IL-4信号转导和功能活性的丧失。缺乏IL-4Rα导致感染巴西尼波斯特龙寄生虫后TH2反应显著减弱，但并不是没有。从未感染的TL-4Rα(-/-)小鼠分离出CD4(+)、CD62L-HIGH和CD62L-Low T细胞群，经T细胞受体交联性刺激后，CD62L-Low细胞分泌相当数量的IL-4，而CD62L-HIGH细胞分泌相当数量的IL-4，在有或没有IL-4的情况下，经抗CDS培养4天后显著增强。从IL-4Rα(-/-)、β(2)-微球蛋白(-/-)双纯合子小鼠分离的CD62L-low细胞产生的IL-4少于IL-4Rα(-/-)或野生型小鼠。这些结果表明，CD62L-低CD4(+)人群体内存在一条IL-4不依赖的、β(2)-微球蛋白依赖的途径，通过该途径获得了产生IL-4的能力，这有力地表明这些细胞是NK T细胞。
IL-4 receptor alpha chain (IL-4R alpha)-deficient mice were generated by gene-targeting in BALB/c embryonic stem cells. Mutant mice showed a loss of IL-4 signal transduction and functional activity. The lack of IL-4R alpha resulted in markedly diminished, but not absent, TH2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis. CD4(+), CD62L-high, and CD62L-low T cell populations from uninfected TL-4R alpha(-/-) mice were isolated by cell sorting, Upon primary stimulation by T cell receptor cross-linkage, the CD62L-low, bur not the CD62L-high, cells secreted considerable amounts of IL-4, which was strikingly enhanced upon 4-day culture with anti-CDS in the presence or absence of IL-4. CD62L-low cells isolated from IL-4R alpha(-/-), beta(2)-microglobulin(-/-) double homozygous mice produced less IL-4 than did either IL-4R alpha(-/-) or wild-type mice. These results indicate that an IL-4-independent, beta(2)-microglobulin-dependent pathway exists through which the CD62L-low CD4(+) population has acquired IL-4-producing capacity in vivo, strongly suggesting that these cells are NK T cells.