ACCELERATION OF INFLUENZA-VIRUS CLEARANCE BY TH1 CELLS IN THE NASAL SITE OF MICE IMMUNIZED INTRANASALLY WITH ADJUVANT-COMBINED RECOMBINANT NUCLEOPROTEIN

The protective roles of influenza viral nucleoprotein (NP), together w ith the cellular mechanism of the protection in the nasal site, were e xamined in BALB/c mice immunized intranasally with an adjuvant (choler a 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 accel erated virus clearance from the nasal site in both an influenza type-s pecific 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 s urvival rate after challenge with a lethal dose of virus in mice immun ized and boosted with adjuvant-combined NP. The acceleration of nasal virus clearance was accompanied with acceleration of type-specific sys temic delayed-type hypersensitivity (DTH) and with IFN-gamma productio n by nasal lymphocytes. The nasal lymphocytes from the immunized and c hallenged mice generated a significantly high level of DTH when transf erred locally, but no class 1 MHC-restricted CTL response. Moreover, n asal CD4(+) T cells, induced by NP immunization and increased in numbe r by the subsequent challenge, were involved in the accelerated IFN-ga mma production. These results suggest that nasal Th1 cells, capable of producing IFN-gamma and mediating DTH, are involved in the type-speci fic acceleration of recovery from influenza after challenge in mice im munized intranasally with adjuvant-combined NP, although the nonspecif ic mechanism of accelerated recovery remains to be solved.