Cell-mediated immune response to porcine reproductive and respiratory syndrome virus.

摘要

The cell-mediated immune (CMI) response of pigs to porcine reproductive and respiratory syndrome virus (PRRSV) is low in magnitude and appears late after infection. The ability of PRRSV to suppress CMI response is not known. We reported in this dissertation that PRRSV has the ability to significantly suppress CD25, interferon gamma (IFNgamma), and tumor-necrosis factor alpha expression by T cells in response to concanavalin A and phorbol 12-myristate 13-acetate plus ionomycin, respectively. The suppressive ability of PRRSV associated with PRRSV virulence and type of myeloid antigen-presenting cells the virus infect. Virulent PRRSV significantly suppressed T cell response, whereas attenuated PRRSV did not. Monocytes supported T cell suppression more effectively than monocyte-derived macrophages and immature monocyte-derived dendritic cells. T cell suppression negatively associated with increased interleukin-10 (IL-10) gene expression. Neutralization of IL-10 activity by anti-swine IL-10 monoclonal antibodies inhibited T cell suppression.; PRRSV modified-live Virus (MLV) vaccine is currently used in the field to control diseases caused by PRRSV. To enhance CMI response to PRRSV MLV vaccine, five different vaccine adjuvants (bacterial endotoxin-derived adjuvant, mixed open reading frame 5 (ORF5) peptides derived from 5 PRRSV isolates, porcine IFNalpha, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose, and porcine IL-12) were studied. Administration of mixed ORF5 peptides at 14 and 28 days after PRRS MLV vaccination significantly increased IFNgamma production in CD4-CD8+gammadelta +, CD4-CD8-gammadelta+, and CD4-CD8+gammadelta- T cells. Administration of porcine IL-12 at 1 day after PRRS MLV vaccination significantly increased IFNgamma production in CD4+CD8 +gammadelta-, CD4-CD8+gammadelta +, and CD4-CD8+gammadelta - T cells. Significantly increased IFNgamma expression in CD4 +CD8+gammadelta-, CD4-CD8 +gammadelta+, CD4-CD8+gammadelta - T cells but not CD4-CD8-gammadelta + T cells were correlated significantly with the reduction of lung lesion scores and viremia after virulent PRRSV challenge. Administration of porcine IFNalpha at -1, 0, and 1 day and porcine IL,-12 at 1 day after PRRS MLV vaccination significantly increased CD25 expression in CD4-CD8 +gammadelta+ T cells. However, the increased CD25 expression did not correlate with protection. None of the vaccine adjuvants contributed to the reduction of lung lesion scores and viremia in comparison to PRRS MLV alone.