CELLULAR MECHANISMS INVOLVED IN PROTECTION AND RECOVERY FROM INFLUENZA-VIRUS INFECTION IN IMMUNODEFICIENT MICE

We investigated the role of different lymphocyte subpopulations in the host defense reaction against influenza virus infection, taking advan tage of various immunodeficient mouse strains, Whereas, following immu nization, wild-type animals showed complete protection against challen ge with a lethal dose of A/PR8/34 (PR8) virus, mice that lack both B a nd T cells but not NK cells (namely, scid and RAG2(-/-) mice) did not display any protective effect in similar conditions, By contrast, J(H) D(-/-) mice devoid of B cells and immunized with virus showed a protec tive response after challenge with a lethal dose, The immunized J(H)D( -/-) mice that survived completely recovered from the influenza virus infection. Immunized J(H)D(-/+) mice exhibited a more complete protect ion, suggesting the role of specific antibodies in resistance to infec tion. To assess the role of natural immunity in the host defense again st influenza virus, we carried out experiments with scid mice challeng ed with lower but still lethal doses of PR8 virus. While an increased NK activity and an increased number of NK1.1(+) cells in lungs of scid mice infected with PR8 virus were noted, in vivo depletion of the NK1 .1(+) cells did not affect the overall survival df the mice, Our resul ts show that specific T cells mediate protection and recovery of J(H)D (-/-) mice immunized with live virus and challenged with lethal doses of influenza virus.