Satoskar A R, Stamm L M, Zhang X, Satoskar A A, Okano M, Terhorst C, David J R, Wang B
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston MA 02115, USA.
J Immunol. 1999 Jun 1;162(11):6747-54.
NK cells are believed to play a critical role in the development of immunity against Leishmania major. We recently found that transplantation of wild-type bone marrow cells into neonatal tgepsilon 26 mice, which are deficient in T and NK cells, resulted in normal T cell development, but no or poor NK cell development. Using this novel model we analyzed the role of NK cells in the development of Th1 response and control of cutaneous L. major infection. Mice selectively lacking NK cells (NK-T+) developed an efficient Th1-like response, produced significant amounts of IL-12 and IFN-gamma, and controlled cutaneous L. major infection. Administration of neutralizing IL-12 Abs to NK-T+ mice during L. major infection resulted in exacerbation of the disease. These results demonstrate that NK cells are not critical for development of protective immunity against L. major. Furthermore, they indicate that IL-12 can induce development of Th1 response independent of NK cells in NK-T+ mice following L.major infection.
自然杀伤细胞被认为在针对硕大利什曼原虫的免疫发育中起关键作用。我们最近发现，将野生型骨髓细胞移植到缺乏T细胞和自然杀伤细胞的新生tgepsilon 26小鼠体内，可导致正常的T细胞发育，但自然杀伤细胞发育不良或未发育。利用这个新模型，我们分析了自然杀伤细胞在Th1反应发育和皮肤硕大利什曼原虫感染控制中的作用。选择性缺乏自然杀伤细胞的小鼠（NK-T+）产生了有效的Th1样反应，产生了大量的白细胞介素-12和γ干扰素，并控制了皮肤硕大利什曼原虫感染。在硕大利什曼原虫感染期间，给NK-T+小鼠注射中和性白细胞介素-12抗体导致病情加重。这些结果表明，自然杀伤细胞对于针对硕大利什曼原虫的保护性免疫发育并非至关重要。此外，它们表明，白细胞介素-12可在硕大利什曼原虫感染后的NK-T+小鼠中独立于自然杀伤细胞诱导Th1反应的发育。
