Porcine Reproductive and Respiratory Syndrome Virus Persistence in Blood,Spleen,Lymph Nodes,and Tonsils of Experimentally Infected Pigs Depends on the Level of CD8 high T Cells

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) induces a persistent viral infection suggesting an inefficient cellular immune response. The aim of the study was to evaluate the relationship between viral persistence and cytotoxic cells in blood, spleen, mediastinal lymph nodes (MLN) and tonsils of PRRSV experimentally infected pigs. Groups of four to six specific pathogen-free (SPF) pigs were infected with the LHVA-93-3 isolate, and blood and lymphoid organs were collected from 3 to 60 days post-infection (p.i.). Infectious particles and viral RNA were more or less rapidly eliminated in serum, spleen, lungs and MLN but persisted the longest in tonsils. Lymphocytes CD2⁺ CD4⁺, CD2⁺ CD8^high, CD2⁺ CD8^low and NK cells populations were phenotyped and their reactivity to PHA and ConA were tested. Analysis of T cell subsets in blood and lymphoid organs indicated that the percentages of CD2⁺ CD8⁺ T cells slightly increased in spleen at 17 days p.i, whereas no changes were observed in CD2⁺ CD4⁺ cells in blood or lymphoid organs. However, discrimination of CD8⁺ cells in CD8^high and CD8^low subsets revealed that the percentages of CD2⁺ CD8^high cells increased in spleen and blood from 10 to 45 or 60 days p.i. while they transiently increased in MLN and decreased in tonsils. The CD8^low/CD8^high ratio increased in the blood of PRRSV-infected animals at three days p.i. due to a transient decrease of CD2⁺ CD8^high cells. This same ratio decreased in the spleen of infected pigs from 10 to 45 days p.i. due to an increase of CD2⁺ CD8^high cells. The CD2⁺ MIL-4⁺ cell subset(NK cells) was not significantly modified in blood or lymphoid organs. In addition, the ability of lymphoid T cells from blood and lymphoid organs to respond to ConA or PHA stimulation was transiently impaired in blood and spleen during the PRRSV persistent infection. Taken together, these results suggest that, in persistently infected pigs, an impaired CD2⁺ CD8^high cell response in MLN and tonsils favors viral persistence in these organs, in contrast with the response seen in blood and spleen where viral elimination appears to occur sooner.