Effects of Porcine Reproductive and Respiratory Syndrome Virus-Infected Antigen-Presenting Cells on T Cell Activation and Antiviral Cytokine Production

The ability of porcine reproductive and respiratory syndrome virus (PRRSV) to suppress T cell expression of CD25 (α chain of interleukin [IL]-2 receptor), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) was determined by flow cytometry in naive porcine T cells in response to mitogen(concanavalin A) and cytokine inducers (phorbol 12-myristate 13-acetate plus ionomycin [PMA/I]). Four PRRSV isolates of varying clinical virulence and three different types of porcine myeloid antigen-presenting cells (APCs) were used. T cells cultured with monocytes infected with virulent PRRSV (VR-2385, SDSU-73, and VR-2332), but not with a vaccine strain (Ingelvac PRRS MLV; Boehringer Ingelheim Vetmedica, St. Joseph, MO), demonstrated significantly reduced CD25 expression (%CD25⁺) and IFN-γ expression (%IFN-γ ⁺) compared with T cells incubated with uninoculated monocyte cultures. T cells cultured with monocytes infected with all four PRRSV isolates demonstrated significantly reduced %TNF-α ⁺. The significant reduction of %CD25⁺, %IFN-γ ⁺, and %TNF-α ⁺ was not detected in T cells cultured with monocyte-derived macrophages (MDMs) and immature monocyte-derived dendritic cells (MDCs) infected with any PRRSV isolates. Heat-inactivated PRRSV did not induce significantly reduced T cell responses in any APC cultures. The reduction of T cell response in monocyte cultures was not due to PRRSV-induced T cell death. Gene expression of IL-10 detected by semiquantitative reverse transcriptase-polymerase chain reaction was significantly increased in virulent PRRSV-infected monocyte cultures after PMA/I, but not concanavalin A, stimulation compared with IL-10 gene expression from uninoculated monocyte cultures. Increased IL-10 gene expression contributed to significantly reduced %IFN-γ ⁺ and %TNF-α ⁺, but not %CD25⁺, as determined by IL-10 neutralization assay. This study reports that PRRSV has the ability to suppress T cell responses. The suppressive ability of PRRSV is associated with viral virulence and is mediated by virus-infected monocytes, but not by virus-infected MDMs and immature MDCs.