INTERLEUKIN-4 CAUSES DELAYED VIRUS CLEARANCE IN INFLUENZA VIRUS-INFECTED MICE

Two different subsets of T cells, Th1 and Th2 cells, have been demonst rated to secrete different profiles of cytokines and to influence vari ous infections in different ways, Whereas cytokines secreted by Th1 ce lls, particularly gamma interferon, promote the generation of cell-med iated immunity, Th2 cells and their cytokines (interleukin-4 [IL-4], I L-5, IL-10, and IL-13) have been shown to function in recovery from pa rasitic infections and in antibody responses, In this study, we analyz ed the effects of the dominant Th2 cytokine, IL-4, on immunity to viru s infection, We assessed the effects of IL-4 on both secondary immune responses by an adoptive transfer assay and primary immune responses b y in vivo treatment of influenza virus-infected mice with IL-4. The re sults demonstrated that IL-4 can function to inhibit antiviral immunit y at both stages, We found that IL-4 treatment of sensitized cells dur ing secondary stimulation in vitro had little effect on their ability to lyse virus-infected target cells in a Cr-51 release assay, Neverthe less, the clearance of influenza A/PR/8/34 (H1N1) virus from the lungs of infected BALB/c mice was significantly delayed after the transfer of virus-specific T cells secondarily stimulated in the presence of IL -4 in comparison to virus clearance in recipients of cells stimulated in the absence of IL-4, In contrast to the adoptive transfer results, the treatment of PR8 virus-infected mice,vith IL-4 during primary infe ction greatly suppressed the generation of cytotoxic T-cell precursors , as assessed by secondary stimulation in vitro, In addition, culture supernatants of secondarily stimulated spleen cells from IL-4-treated mice contained significantly less gamma interferon and more IL-4 than did spleen cells from controls, More importantly, the treatment of mic e with IL-4 resulted in an extremely significant delay in virus cleara nce, Thus, IL-4 can inhibit both primary and secondary antiviral immun e responses.