Reinfection of an influenza A virus seropositive host with another strain A or homologous virus occurs in both humans and experimental animal models and provides an opportunity to investigate lymphokine regulation of secondary antiviral cell- mediated immunity. The use of an experimental animal model of reinfection provides opportunity to study the immunobiology of the antiviral responses at the site where the antigen is replicating (lungs) and in the regional (mediastinal) lymph node. The long term objective is two-fold: 1) to determine why, following resolution of an influenza viral infection, the seropositive host may still be susceptible to infection with the same strain of serotype of virus; and 2) to determine the operative immunologic mechanism(s) which prevents the expression of a DTH response in lungs of an influenza (A/Bangkok) seropositive host following reinfection with a second (A/PR8) strain A virus. With regard to the first objective, while it is likely that antigenic differences in the homologous virus are responsible for some susceptibility to reinfection, we hypothesize that components of the seropositive host's immune response actually facilitate reinfection and promote limited virus replication upon re- exposure to homologous virus. Further, we propose that the host mechanism which facilitates reinfection, also functions to prevent expression of a delayed-type hypersensitivity (DTH) in lungs of an influenza A seropositive host following reinfection with another strain A virus. The absence of a DTH response in the lungs of an A/Bangkok primed mouse reinfected with A/PR8 reflects the activation of an immunologic mechanism that suppresses the expression of the DTH. The immunologic mechanism appears to involve a small molecular weight protein termed a """"""""contralymphokine"""""""" which prevents the expression, but not the production of, lymphokines associated with DTH. In the mouse influenza reinfection model, we have detected a contralymphokine, produced by mononuclear cells in response to viral antigen stimulation, which interferes with the expression of LIF in a migration assay, IL2 in an NK enhancement assay, and IL2 in a proliferation (CTLL-20) assay. In this proposal, the contralymphokine will be purified, characterized and its mechanism of action determined in the LIF migration assay and the IL2 CTLL-20 proliferation assay. These studies will provide information on the regulation of lymphokine expression during viral reinfection of a primed host.
