HETEROSUBTYPIC IMMUNITY TO INFLUENZA TYPE-A VIRUS IN MICE - EFFECTOR MECHANISMS AND THEIR LONGEVITY

Immunity that cross-reacts between influenza type A viruses of distinc t subtypes is called hetero(sub)typic (Het-I). We have studied Het-I b y challenging PR8-immune mice with the heterosubtypic virus X31. Het-I did not prevent infection by X31 but, at its height, strongly aided i n recovery. The nature of the effector mechanisms involved was investi gated by simultaneous challenge with X31 and an immunologically unrela ted influenza type B virus and by depleting individual lymphocyte subs ets in PR8-immune mice before challenge. The study showed the followin g: 1) The effector mechanisms were intimately associated with immune r ecognition events. 2) in the nose, depletion of CD8(+) or CD4(+) T cel ls led to partial reduction of Het-I, and simultaneous depletion of bo th T cell subsets abrogated Het-I almost completely. This T cell-media ted immunity was short lived and had disappeared 4 to 5 mo after induc tion. 3) In trachea and lung, depletion of CD8(+) T cells led to a par tial reduction of Het-I, whereas depletion of CD4(+) T cells was witho ut significant effect. The CD8-mediated component appeared short lived , whereas the residual immunity (in CD4/8-depleted mice) was long live d and persisted past 7 mos after induction. 4) Depletion of NK cells d id not significantly reduce the strength of Het-I in either nose or lu ng. In conclusion, the study shows that Het-I in this system is mediat ed by a complex combination of immune mechanisms that differ, in part, between upper and lower respiratory tract.