Interleukin-4 diminishes CD8(+) respiratory syncytial virus-specific cytotoxic T-lymphocyte activity in vivo.
Although interleukin-4 (IL-4) has been implicated in respiratory syncytial virus (RSV)-enhanced disease, the mechanism by which it modulates immune responses to primary RSV infection remains unclear. We have developed a system to investigate the effect of IL-4 on RSV epitope-specific cytotoxic T-lymphocyte (CTL) effector function in vivo, using an H-2K(d)-restricted RSV M2 epitope. BALB/c mice were infected with recombinant vaccinia virus (rVV) constructed to express RSV M2 protein (vvM2) alone or coexpress M2 and IL-4 (vvM2/IL-4). Splenocytes were assessed for M2-specific CTL activity in a direct (51)Cr release assay and intracellular gamma interferon (IFN-gamma) production by fluorescence-activated cell sorting analysis. Mice infected with vvM2/IL-4 had less M2-specific primary CTL activity than those infected with vvM2. M2-specific CTL frequency, as measured by M2 peptide-induced intracellular IFN-gamma production, was diminished in the vvM2/IL-4 group, partially accounting for the reduction of CTL activity. Mice immunized with either construct were challenged intravenously with RSV 4 weeks postimmunization, and direct CTL were measured. These results demonstrate that local expression of IL-4, at the time of antigen presentation, diminishes the cytolytic activity of primary and memory CD8(+) RSV-specific CTL responses in vivo.
Aung
S
S
Department of Microbiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Tang
Y W
YW
Graham
B S
BS
D000818:Animals; D015153:Blotting, Western; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005434:Flow Cytometry; D015707:HN Protein; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D015707:HN Protein; D010455:Peptides; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G; D015847:Interleukin-4