Selective suppression of the cytotoxic T cell response to influenza virus in mice

Abstract

Mice injected with inactivated (UV light-irradiated) influenza virus produce specific antibody, become sensitized for a delayed-type hypersensitivity reaction, but do not generate specific cytotoxic T (Tc) cells. If injected 4-5 days later with infectious virus, the formation of Tc cells is suppressed by > 90%. If A strain viruses are used, the suppression observed is cross-reactive within A strain viruses but does not extend to B/LEE or to Sendai virus. Serum from mice injected with UV-irradiated virus contains antibodies which on adoptive transfer can inhibit Tc cell formation when infectious homologous virus is used to challenge the recipients. Spleen cells from the same mice, upon adoptive transfer, also inhibit (50-70%) Tc cell formation if transferred within 24 h of injection of infectious virus, and the specificity pattern observed is cross-reactive within A strains. The activity of the cells mediating suppression is destroyed by monospecific anti-Thy-1.2 antibody and complement. The immune cells require I region sharing between donor and recipient mice for their suppressor activity to be effective. (There is also a partial requirement for K, D region sharing, but the possible rejection of transferred cells is not excluded.) Dilution assays in which clonal expansion of Tc precursors is used to estimate their frequency and the presence of T helper (Th) cells indicate that suppressed mice possess Tc precursors and primed cells which, upon restimulation, act as Th cells. Furthermore, injection of irradiated Th cells with inactivated virus does not significantly reduce the ensuing suppression.

Vaccination with inactivated influenza A virus during pregnancy protects neonatal mice against lethal challenge by influenza A viruses representing three subtypes

“…Nonlethal influenza virus infection in the mouse induces subtype cross-reactive protection. Since subtype cross-reactive antibodies have generally not been found, this protection has been attributed to T cells (2,5,14). In the present study, neutralizing-antibody titer to other subtypes was detected when high-dose vaccine was given or when serum complement was added to increase the sensitivity of the assay; in preliminary studies, we have also detected immunoglobulin G antibodies reactive against all three influenza virus subtypes in a sensitive radioimmunoassay.…”

Respiratory syncytial virus

“…Thus, passively acquired antibody could block the induction of Tc, which may be important in recovery from infection, as seen in influenza virus infections (161). Thus, passively acquired antibody could block the induction of Tc, which may be important in recovery from infection, as seen in influenza virus infections (161).…”

Vaccines for the Future?

“…This results in the formation of antibody but only I region-restricted T cell responses are generated, in particular, Th cell formation and I region-restricted DTH responses (Leung, Ada andMcKenzie, 1980a;Leung, Mak and Ada, 1981). If injected intravenously, it may also induce the formation of T cells which suppress the formation of Tc cells (Leung et al, 1980b), which in the mouse are K,D region-restricted in their generation and performance. One exception to this finding is the paramyxovirus, Sendai virus, which normally contains a fusion (F) protein.…”