Functional impairment of PRRSV-specific peripheral CD3⁺CD8^highcells

Abstract

The replication of porcine reproductive and respiratory syndrome virus (PRRSV) in lungs and lymphoid tissues of PRRSV-infected pigs is already strongly reduced before the appearance of neutralizing antibodies, indicating that other immune mechanisms are involved in eliminating PRRSV at those sites. This study aimed to determine whether PRRSV Lelystad virus (LV)-specific cytotoxic T-lymphocytes (CTL) can efficiently eliminate PRRSV-infected alveolar macrophages. Therefore, CTL assays were performed with PRRSV-infected alveolar macrophages as target cells and autologous peripheral blood mononuclear cells (PBMC) from PRRSV-infected pigs as a source of PRRSV-specific CTL. PBMC of 3 PRRSV-infected pigs were used either directly in CTL assays, or following restimulation in vitro. CTL assays with pseudorabies virus (PRV) Begonia-infected alveolar macrophages and autologous PBMC, from 2 PRV Begonia-inoculated pigs, were performed for validation of the assays. In freshly isolated PBMC, derived from PRRSV-infected pigs, CTL activity towards PRRSV-infected macrophages was not detected until the end of the experiment (56 days post infection – dpi). Restimulating the PBMC with PRRSV in vitro resulted in proliferation of CD3+CD8high cells starting from 14 dpi. Although CD3+CD8high cells are generally considered to be CTL, CTL activity was not detected in PRRSV-restimulated PBMC of the 3 pigs until 49 dpi. A weak PRRSV-specific CTL activity was observed only at 56 dpi in PRRSV-restimulated PBMC of one pig. In contrast, a clear CTL activity was observed in PRV Begonia-restimulated PBMC, derived from PRV Begonia-infected pigs, starting from 21 dpi. This study indicates that PBMC of PRRSV-infected pigs contain proliferating CD3+CD8high cells upon restimulation in vitro, but these PBMC fail to exert CTL activity towards PRRSV-infected alveolar macrophages.

Comparative analysis of immune responses following experimental infection of pigs with European porcine reproductive and respiratory syndrome virus strains of differing virulence

“…A relationship between viral clearance and cytotoxic T cells has been previously observed in pigs infected with European and American genotype strains (Lamontagne et al, 2003;Gó mez-Laguna et al, 2009). However, others failed to show that CD3 + CD8 high cells exert CTL activity toward LV-infected alveolar macrophages (Costers et al, 2009). Further studies should determine whether the PRRSV-specific cytotoxic T cell activity in vivo is involved in viral clearance.…”

Innate and adaptive immunity against Porcine Reproductive and Respiratory Syndrome Virus

“…Temporary depletion of CD8+ T cells at the time of infection did not lead to an increase in infection, suggesting that cytotoxic T cells do not have a functional role in control of acute infection (Lohse et al, 2004). Similarly, CTL activity was not detected against PRRSVinfected macrophages until after viremia was cleared (Costers et al, 2009). Memory CTL proliferation was observed at 14 days after infection but CTL activity was not detected until 49 days after infection (Costers et al, 2009).…”

“…Similarly, CTL activity was not detected against PRRSVinfected macrophages until after viremia was cleared (Costers et al, 2009). Memory CTL proliferation was observed at 14 days after infection but CTL activity was not detected until 49 days after infection (Costers et al, 2009). These data suggest that CTL may be involved in the clearance of PRRSV-infected cells in tissues.…”

Recognition of Highly Diverse Type-1 and -2 Porcine Reproductive and Respiratory Syndrome Viruses (PRRSVs) by T-Lymphocytes Induced in Pigs after Experimental Infection with a Type-2 PRRSV Strain

“…In addition, neutralizing antibodies did not provide protection against heterologous challenge [32]. Several studies have found that immunization with live attenuated and killed PRRSV vaccines reduced clinical disease and/or viremia in pigs after PRRSV challenge, before the appearance of neutralizing antibody responses [29,30,33,35–37]. These observations, as well as the co-existence of infectious PRRSV and low titer neutralizing antibodies in the blood of infected pigs [27,28,38,39], lead to the conclusion that neutralizing antibodies alone are not potent enough to control PRRSV infection in pigs recovered from natural infections or vaccinated pigs.…”