Role of Interleukin-4 (IL-4), IL-12, and Gamma Interferon in Primary and Vaccine-Primed Immune Responses to Friend Retrovirus Infection

Abstract

The immunological resistance of a host to viral infections may be strongly influenced by cytokines such as interleukin-12 (IL-12) and gamma interferon (IFN-␥), which promote T helper type 1 responses, and IL-4, which promotes T helper type 2 responses. We studied the role of these cytokines during primary and secondary immune responses against Friend retrovirus infections in mice. IL-4-and IL-12-deficient mice were comparable to wild-type B6 mice in the ability to control acute and persistent Friend virus infections. In contrast, more than one-third of the IFN-␥-deficient mice were unable to maintain long-term control of Friend virus and developed gross splenomegaly with high virus loads. Immunization with a live attenuated vaccine virus prior to challenge protected all three types of cytokine-deficient mice from viremia and high levels of spleen virus despite the finding that the vaccinated IFN-␥-deficient mice were unable to class switch from immunoglobulin M (IgM) to IgG virus-neutralizing antibodies. The results indicate that IFN-␥ plays an important role during primary immune responses against Friend virus but is dispensable during vaccine-primed secondary responses.

Effective Postexposure Treatment of Retrovirus-Induced Disease with Immunostimulatory DNA Containing CpG Motifs

“…As in most other viral infections, the effective immune response against Friend virus is dominated by a Th1-type activation of the immune system, including the production of IFN-␥ and the activity of cytotoxic T cells (CTL) (8,26). Here we show that a Th1-type response can be amplified by CpG-ODN during an initial retroviral infection to ultimately prevent the onset of lethal disease.…”

Temporal Effects of Gamma Interferon Deficiency on the Course of Friend Retrovirus Infection in Mice

“…To detect FV infection, cells were stained with tissue culture supernatant containing monoclonal antibody (MAb) 34 (7), which is specific for F-MuLV glycosylated Gag protein. MAb 34 binding was detected with allophycocyanin-labeled goat anti-mouse IgG2b-specific antiserum (Caltag Laboratories, Burlingame, Calif.) that was preabsorbed with naive mouse spleen cells to remove background activity (13). Directly labeled fluorescent antibodies specific for Ter119 (Ly-76), CD4, CD8, CD19, and CD43 were obtained from Pharmingen (San Diego, Calif.).…”

Preinfection Treatment of Resistant Mice with CpG Oligodeoxynucleotides Renders Them Susceptible to Friend Retrovirus-Induced Leukemia

“…For example, mice of the H-2 b/b haplotype are resistant to FV-induced disease because they mount lymphocyte responses that appear earlier and are of higher magnitude than those of mice with an H-2 a/b haplotype, which are susceptible to FV-mediated leukemia (8,21). Immunity to FV is associated with a Th1-type immune response, including the production of gamma interferon and the activation of T cells (4,21). Since CpG-ODN shift the immune system toward a Th1-dominated response, it was possible that CpG-ODN pretreatment of FV-susceptible mice might induce resistance.…”