The early IL-4 response to Leishmania major and the resulting Th2 cell maturation steering progressive disease in BALB/c mice are subject to the control of regulatory CD4+CD25+ T cells
The early IL-4 response to Leishmania major and the resulting Th2 cell maturation steering progressive disease in BALB/c mice are subject to the control of regulatory CD4+CD25+ T cells
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DOI：
10.4049/jimmunol.169.6.3232
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发表时间：
2002-09-15
影响因子：
4.4
通讯作者：
Tacchini-Cottier, F
中科院分区：
文献类型：
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作者：
Aseffa, A;Gumy, A;Tacchini-Cottier, F
感染硕大利什曼原虫的BALB/c小鼠中Th 2细胞的易感性和发育是由V β 4V α 8 CD 4（+）T细胞响应哺乳动物RACK 1 Ag的利什曼原虫同源物而产生早期IL-4所致。通过在体内消耗这种调节性T细胞群体，研究了CD 4（+）CD 25（+）调节性T细胞在控制这种早期IL-4产生中的作用。耗竭诱导BALB/c小鼠引流淋巴结中IL-4 mRNA的早期爆发增加，并加剧其淋巴结中IL-4 mRNA和蛋白水平升高的疾病进程。我们进一步表明，转移107个耗尽CD 4（+）CD 25（+）调节性T细胞的BALB/c脾细胞使SCID小鼠对感染易感并允许Th 2分化，而用10（7）个对照BALB/c脾细胞重建的SCID小鼠对李斯特菌感染具有抵抗力。并产生了Th 1反应。用抗IL-4的mAb处理用CD 25-耗尽的脾细胞重建的SCID小鼠中感染L major后阻止Th 2极化的发展，并使其对感染具有抗性。这些结果表明，CD 4（+）CD 25（+）调节性T细胞在该感染模型中调节早期IL-4 mRNA和随后Th 2应答的发展中起作用。
Susceptibility and development of Th2 cells in BALB/c mice infected with Leishmania major result from early IL-4 production by Vbeta4V alpha8 CD4(+) T cells in response to the Leishmania homolog of mammalian RACK1 Ag. A role for CD4(+)CD25(+) regulatory T cells in the control of this early IL-4 production was investigated by depleting in vivo this regulatory T cell population. Depletion induced an increase in the early burst of IL-4 mRNA in the draining lymph nodes of BALB/c mice, and exacerbated the course of disease with higher levels of IL-4 mRNA and protein in their lymph nodes. We further showed that transfer of 107 BALB/c spleen cells that were depleted of CD4(+)CD25(+) regulatory T cells rendered SCID mice susceptible to infection and allowed Th2 differentiation while SCID mice reconstituted with 10(7) control BALB/c spleen cells were resistant to infection with L. major and developed a Th1 response. Treatment with a mAb against IL-4 upon infection with L major in SCID mice reconstituted with CD25-depleted spleen cells prevented the development of Th2 polarization and rendered them resistant to infection. These results demonstrate that CD4(+)CD25(+) regulatory T cells play a role in regulating the early IL-4 mRNA and the subsequent development of a Th2 response in this model of infection.