Different immunological requirements for protection against acute versus persistent Friend retrovirus infections.
The propensity of retroviruses to rapidly establish persistent infections poses a formidable problem in vaccination strategies. In the current study, we use a live attenuated vaccine to study protection against acute and persistent Friend virus infections in mice. Adoptive transfers of immune CD8(+) T cells combined with passive immunizations with virus-neutralizing antibodies increased protection against acute disease compared with either treatment alone, but there was no protection against the establishment of persistent infection. In addition, the protection against acute disease elicited by the combination treatment was dependent on endogenous CD4(+) T cells as no protection was achieved in CD4(+) T-cell-depleted mice. Quantitative studies showed that doubling the numbers of immune lymphocytes used in adoptive transfer experiments increased protection against acute disease depending on the type of lymphocyte subset used in the transfer. CD8(+) T cells were the most potent subset for the transfer of such protection. However, even high numbers of immune CD8(+) T cells gave no protection against the establishment of persistent infections. The data indicate that strengthening the numbers of specific immune cell subsets may have a beneficial effect on protection against acute disease, but protection from establishment of persistence requires complex immune responses involving multiple lymphocyte subsets.
Dittmer
U
U
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th Street, Hamilton, Montana 59840, USA.
Hasenkrug
K J
KJ
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D002908:Chronic Disease; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D009500:Neutralization Tests; D012192:Retroviridae Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D013163:Splenomegaly / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology; D014766:Viremia / Q000276:immunology / Q000517:prevention & control / Q000821:virology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines