Immune response to mouse mammary tumor virus in mice lacking the alpha/beta interferon or the gamma interferon receptor.
Mouse mammary tumor virus (MMTV) is a retrovirus which induces a strong immune response and a dramatic increase in the number of infected cells through the expression of a superantigen (SAg). Many cytokines are likely to be involved in the interaction between MMTV and the immune system. In particular, alpha/beta interferon (IFN-alpha/beta) and gamma interferon (IFN-gamma) exert many antiviral and immunomodulatory activities and play a critical role in other viral infections. In this study, we have investigated the importance of interferons during MMTV infection by using mice with a disrupted IFN-alpha/beta or IFN-gamma receptor gene. We found that the SAg response to MMTV was not modified in IFN-alpha/betaR(0/0) and IFN-gammaR(0/0) mice. This was true both for the early expansion of B and T cells induced by the SAg and for the deletion of SAg-reactive cells at later stages of the infection. In addition, no increase in the amount of proviral DNA was detected in tissues of IFN-alpha/betaR(0/0) and IFN-gammaR(0/0) mice, suggesting that interferons are not essential antiviral defense mechanisms during MMTV infection. In contrast, IFN-gammaR(0/0) mice had increased amounts of IL-4 mRNA and an altered usage of immunoglobulin isotypes with a reduced frequency of IgG2a- and IgG3-producing cells. This was associated with lower titers of virus-specific antibodies in serum early after infection, although efficient titers were reached later.
Maillard
I
I
Institute of Microbiology, University of Lausanne, Switzerland.
Launois
P
P
Xenarios
I
I
Louis
J A
JA
Acha-Orbea
H
H
Diggelmann
H
H
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D003433:Crosses, Genetic; D004279:DNA, Viral; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D013997:Time Factors; D014412:Tumor Virus Infections / Q000276:immunology*; D000096743:Interferon gamma Receptor
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D007371:Interferon-gamma; D015847:Interleukin-4; D008565:Membrane Proteins; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon; D018089:Superantigens; D000096743:Interferon gamma Receptor