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Journal of Virology, November 1999, p. 8944-8949, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interleukin-4 Diminishes CD8+ Respiratory Syncytial Virus-Specific Cytotoxic T-Lymphocyte Activity In Vivo

Sandra Aung,1 Yi-Wei Tang,2,3 and Barney S. Graham1,2,*

Departments of Microbiology & Immunology,1 Medicine,2 and Pathology,3 Vanderbilt University School of Medicine, Nashville, Tennessee

Received 12 May 1999/Accepted 15 July 1999

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-2Kd-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 51Cr 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.

* Corresponding author. Mailing address: Vanderbilt University School of Medicine, A-4103 Medical Center North, 1161 21st Ave. South, Nashville, TN 37232-2582. Phone: (615) 343-3717. Fax: (615) 322-8222. E-mail: barney.graham{at}mcmail.vanderbilt.edu.

Journal of Virology, November 1999, p. 8944-8949, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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