Maillard I, Launois P, Himmelrich H, Acha-Orbea H, Diggelmann H, Locksley R M, Louis J A
Institute of Microbiology, University of Lausanne, Lausanne, Switzerland.
Eur J Immunol. 2001 Apr;31(4):1288-96.
Early production of IL-4 by LACK-reactive Vbeta4-Valpha8 CD4(+) T cells instructs aberrant Th2 cell development and susceptibility to Leishmania major in BALB / c mice. This was demonstrated using Vbeta4(+)-deficient BALB / c mice as a result of chronic infection with MMTV (SIM), a mouse mammary tumor virus expressing a Vbeta4-specific superantigen. The early IL-4 response was absent in these mice which develop a Th1 response to L. major. Here, we studied the functional plasticity of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells using BALB/ c mice inoculated with L. major shortly after infection with MMTV (SIM), i. e. before deletion of Vbeta4(+) cells. These mice fail to produce the early IL-4 response to L. major and instead exhibit an IFN-gamma response that occurs within LACK-reactive Vbeta4-Valpha8 CD4(+) T cells. Neutralization of IFN-gamma restores the production of IL-4 by these cells. These data suggest that the functional properties of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells are not irreversibly fixed.
LACK反应性Vβ4-Vα8 CD4(+) T细胞早期产生IL-4会指导BALB/c小鼠中异常的Th2细胞发育以及对杜氏利什曼原虫的易感性。这是通过使用因感染MMTV（SIM，一种表达Vβ4特异性超抗原的小鼠乳腺肿瘤病毒）而慢性感染的Vβ4(+)缺陷型BALB/c小鼠得以证明的。这些小鼠对杜氏利什曼原虫产生Th1反应，且不存在早期IL-4反应。在此，我们使用在感染MMTV（SIM）后不久（即Vβ4(+)细胞缺失之前）接种杜氏利什曼原虫的BALB/c小鼠，研究了LACK反应性Vβ4-Vα8 CD4(+) T细胞的功能可塑性。这些小鼠未能对杜氏利什曼原虫产生早期IL-4反应，而是在LACK反应性Vβ4-Vα8 CD4(+) T细胞内出现了IFN-γ反应。中和IFN-γ可恢复这些细胞产生IL-4的能力。这些数据表明，LACK反应性Vβ4-Vα8 CD4(+) T细胞的功能特性并非不可逆转地固定。
