Tamura S, Miyata K, Matsuo K, Asanuma H, Takahashi H, Nakajima K, Suzuki Y, Aizawa C, Kurata T
Department of Pathology, National Institute of Health, Tokyo, Japan.
J Immunol. 1996 May 15;156(10):3892-900.
The protective roles of influenza viral nucleoprotein (NP), together with the cellular mechanism of the protection in the nasal site, were examined in BALB/c mice immunized intranasally with an adjuvant (cholera toxin B subunit containing 0.2% of the whole toxin)-combined A or B virus recombinant NP. The NP-immune mice, when challenged intranasally with a sublethal dose of the virus 3 wk after immunization, had accelerated virus clearance from the nasal site in both an influenza type-specific and a nonspecific manner, as shown by the protection from high morbidity from the second day after challenge. Both type-specific and nonspecific acceleration of recovery was confirmed by the increased survival rate after challenge with a lethal dose of virus in mice immunized and boosted with adjuvant-combined NP. The acceleration of nasal virus clearance was accompanied with acceleration of type-specific systemic delayed-type hypersensitivity (DTH) and with IFN-gamma production by nasal lymphocytes. The nasal lymphocytes from the immunized and challenged mice generated a significantly high level of DTH when transferred locally, but no class I MHC-restricted CTL response. Moreover, nasal CD4+ T cells, induced by NP immunization and increased in number by the subsequent challenge, were involved in the accelerated IFN-gamma production. These results suggest that nasal Th1 cells, capable of producing IFN-gamma and mediating DTH, are involved in the type-specific acceleration of recovery from influenza after challenge in mice immunized intranasally with adjuvant-combined NP, although the nonspecific mechanism of accelerated recovery remains to be solved.
用佐剂（含0.2%全毒素的霍乱毒素B亚单位）联合A或B病毒重组核蛋白（NP）经鼻内免疫BALB/c小鼠，研究流感病毒核蛋白（NP）的保护作用及其在鼻部位的细胞保护机制。NP免疫小鼠在免疫后3周经鼻内用亚致死剂量病毒攻击时，从攻击后第二天起对高发病率有保护作用，表明其以流感病毒型特异性和非特异性方式加速了病毒从鼻部位的清除。用佐剂联合NP免疫和加强免疫的小鼠，在经致死剂量病毒攻击后存活率增加，证实了恢复的型特异性和非特异性加速。鼻病毒清除的加速伴随着型特异性全身迟发型超敏反应（DTH）的加速和鼻淋巴细胞产生干扰素-γ。免疫和攻击小鼠的鼻淋巴细胞局部转移时产生显著高水平的DTH，但无I类MHC限制性CTL反应。此外，NP免疫诱导并在随后攻击中数量增加的鼻CD4+T细胞参与了干扰素-γ产生的加速。这些结果表明，能够产生干扰素-γ并介导DTH的鼻Th1细胞参与了用佐剂联合NP经鼻内免疫的小鼠在攻击后流感恢复的型特异性加速，尽管加速恢复的非特异性机制仍有待解决。
