Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo.
AUTOR(ES)
Sharma, D P
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=190762Documentos Relacionados
- Interleukin-4 Diminishes CD8+ Respiratory Syncytial Virus-Specific Cytotoxic T-Lymphocyte Activity In Vivo
- Vaccinia virus-specific human CD4+ cytotoxic T-lymphocyte clones.
- Evolution of Vaccinia Virus-Specific CD8+ Cytotoxic T-Lymphocyte Responses in Primary Vaccinees and Revaccinees
- Cytotoxic T-Lymphocyte Antigen 4 Gene and Recovery from Hepatitis B Virus Infection
- Association between Virus-Specific Cytotoxic T-Lymphocyte and Helper Responses in Human Immunodeficiency Virus Type 1 Infection