Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo

被引:119
作者
Sharma, DP [1 ]
Ramsay, AJ [1 ]
Maguire, DJ [1 ]
Rolph, MS [1 ]
Ramshaw, IA [1 ]
机构
[1] AUSTRALIAN NATL UNIV,JOHN CURTIN SCH MED RES,VIRAL ENGN & CYTOKINE RES GRP,CANBERRA,ACT 2601,AUSTRALIA
关键词
D O I
10.1128/JVI.70.10.7103-7107.1996
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Interleukin-4 (IL-4) promotes the growth of Th2-type cells while down regulating the development of Th1-type cells. It has been suggested that the actions of this factor inhibit Th1-type effector activity in vivo and may underlie the development of diseases normally controlled by cell-mediated immune responses. Here, we show that clearance of recombinant vaccinia viruses (VV) engineered to express the gene for murine IL-4 is markedly delayed in mice compared with control recombinant VV, While antiviral antibody levels and NK activity in mice given control virus or IL-4-expressing virus were similar, antiviral cytotoxic T-lymphocyte responses were profoundly suppressed throughout the course of infection with the latter, Limiting dilution analysis of IL-4-virus-infected spleens revealed a marked reduction in numbers of cytotoxic T-lymphocyte precursors, Furthermore, reverse transcriptase PCR analysis of splenic mRNA prepared from mice infected with the IL-4 expressing VV showed a marked down regulation of IL-12, gamma interferon, and IL-2 gene expression compared with that from mice given control virus, IL-4 also inhibited the production of nitric oxide (NO), a potent mediator of antimicrobial activity, Together, these data show that IL-4 markedly suppresses the development of antiviral cell-mediated immune responses in vivo with deleterious effects on virus clearance.
引用
收藏
页码:7103 / 7107
页数:5
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