Role of interleukin-4 (IL-4), IL-12, and gamma interferon in primary and vaccine-primed immune responses to Friend retrovirus infection.
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-gamma), 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-gamma-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-gamma-deficient mice were unable to class switch from immunoglobulin M (IgM) to IgG virus-neutralizing antibodies. The results indicate that IFN-gamma plays an important role during primary immune responses against Friend virus but is dispensable during vaccine-primed secondary responses.
Dittmer
U
U
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Peterson
K E
KE
Messer
R
R
Stromnes
I M
IM
Race
B
B
Hasenkrug
K J
KJ
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology; D018664:Interleukin-12 / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology; D007942:Leukemia, Experimental / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D012192:Retroviridae Infections / Q000276:immunology* / Q000821:virology; D013154:Spleen / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology; D014611:Vaccination / Q000379:methods; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia / Q000821:virology
D000914:Antibodies, Viral; D016207:Cytokines; D014765:Viral Vaccines; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma