Thymocyte and Peripheral Blood T Lymphocyte Subpopulation Changes in Piglets Following in Utero Infection with Porcine Reproductive and Respiratory Syndrome Virus

Abstract

Piglets infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV) are born severely immunocompromised. In this article we more closely examine the effects of in utero PRRSV infection on circulating and thymic T cell populations. Numbers of CD4+, CD8+, and dual-positive lymphocytes were quantitated in circulation and in the thymus during the 2 weeks following birth. At birth we found that the number of circulating lymphocytes was suppressed by 60%. Lymphocyte numbers were also suppressed by 42% at day 7, but by day 14 the number of lymphocytes had rebounded and was actually 47% greater than controls. At birth and day 7, a drop in the number of CD4+ cells could partially explain the suppression we observed, while the rebound in total lymphocyte numbers seen at day 14 was due to a nearly fourfold increase in the number of circulating CD8+ cells. As a result, the normal CD4+:CD8+ ratio of between 1.4 and 2.2 for neonatal pigs was reduced to 0.1-0.5. The thymuses of infected piglets were found to be 50% smaller than those of control pigs and were characterized by cortical involution and severe cortical depletion of thymocytes. Analysis of the population of thymocytes revealed that double-positive thymocytes were suppressed to a greater degree than either single positive subpopulation. In addition, we show that the number of thymocytes undergoing apoptosis was increased twofold in piglets infected with PRRSV. Taken together, these results help explain the dramatic immunosuppression observed in neonatal animals infected in utero with PRRSV.

Thymic depletion of lymphocytes is associated with the virulence of PRRSV-1 strains

“…Atrophy and depletion of the thymus in piglets infected with PRRSV-2 strains of different virulence have been associated with a loss of T cells in the cortex of the thymus and direct or indirect induction of apoptotic phenomena (Feng et al, 2002;He et al, 2012;Li et al, 2014). In our study all infected animals, independently of the PRRSV-1 strain used, showed changes in the histomorphometry of the thymus and significant amounts of apoptosis was detected.…”

“…and has been suggested to play a significant role in PRRSV infection, with increased apoptotic cells widely distributed within both PRRSV-1 and PRRSV-2 infected tissues (Feng et al, 2002;Labarque et al, 2003;Wang et al, 2011;Gómez-Laguna et al, 2012;He et al, 2012;Li et al, 2014;Morgan et al, 2014;Rodríguez-Gómez et al, 2014).…”

“…The infected cells may interact with thymocytes delivering pro-apoptotic signals (He et al, 2012;Li et al, 2014). Several cytokines including TNF-α and IL-1α/β, promote apoptosis of T cell lines (Feng et al, 2002;Salguero et al, 2005). In addition, during the course of PRRSV, infected macrophages and, to a lesser extent neutrophils and lymphocytes, have been shown to up-regulate the expression of IL-1α, IL-6 and TNF-α (Labarque et al, 2003;Gómez-Laguna et al, 2010;Barranco et al, 2012).…”

“…A decrease in the relative thymus weight, associated to a decreased cellularity in the cortex and less commonly in the medulla, is a sensible indicator for immunosuppresion (Elmore, 2006;Pearse, 2006aPearse, , 2006b. Cortical involution of the thymus with a poor demarcation of cortico-medullary boundary and apoptosis of cortical thymocytes have been reported in PRRSV-2 infected piglets but data for PRRSV-1 strains are very scarce (Feng et al, 2002;Wang et al, 2011;He et al, 2012;Li et al, 2014).…”

Membrane markers of the immune cells in swine: an update

“…Specific identification of the various subpopulations of leukocytes enables improved investigations of the immune response to various porcine infections such as Actinobacillus pleuropneumoniae, African swine fever virus, classical swine fever virus, porcine reproductive and respiratory syndrome virus (PRRSV) and Aujeszky disease virus [6, 41,76,110,116,127,137,213]. An understanding of these interactions is essential for the development of new generations of vaccines.…”