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 (alpha chain of interleukin [IL]-2 receptor), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) 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-gamma expression (%IFN-gamma (+)) compared with T cells incubated with uninoculated monocyte cultures. T cells cultured with monocytes infected with all four PRRSV isolates demonstrated significantly reduced %TNF-alpha (+). The significant reduction of %CD25(+), %IFN-gamma (+), and %TNF-alpha (+) 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-gamma (+) and %TNF-alpha (+), 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.
Charerntantanakul
Wasin
W
Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
Platt
Ratree
R
Roth
James A
JA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000821:virology; D015536:Down-Regulation; D015870:Gene Expression; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008264:Macrophages / Q000821:virology; D009000:Monocytes / Q000502:physiology / Q000821:virology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000472:pathogenicity / Q000502:physiology*; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014774:Virulence
D053645:Interleukin-2 Receptor alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma