Characterization of naturally occurring severe combined immunodeficiency (SCID) in a line of pigs and their response to porcine reproductive and respiratory syndrome virus (PRRSV) infection

Doctor of PhilosophyDiagnostic Medicine/PathobiologyRaymond R. R. RowlandSevere combined immunodeficiency (SCID) is a rare group of inherited disorders characterized by defects in both humoral and cellular immune functions. Naturally occurring SCID has been first described in humans in the 1960s and subsequently identified in horses, mice, and dogs, but never before in pigs. Affected animals are characterized by having loss of functional B and T lymphocytes, and in some cases natural killer (NK) cells, but normal numbers of monocytes, granulocytes, and megakaryocytes. As a result, affected animals fail to produce antibodies and succumb to common disease pathogens after circulating maternal antibodies decay. SCID models are extremely valuable for the understanding of molecular mechanisms of immunological processes during viral and bacterial diseases, cancer, and autoimmunity. SCID mice are widely used as the current model; however, the relevance of the murine SCID model to human and veterinary immune research is limited and there is an increasing need for a more representative model of SCID is imperative. We describe the gross, microscopic, and immunophenotypic characteristics of a line of Yorkshire pigs having naturally occurring SCID. Affected pigs lack T and B lymphocytes, but display circulating NK cells, fail to produce antibodies to viral infection, and lack cell-mediated response to tumor xenotransplants. We also describe response of SCID pigs to porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV is the most devastating virus in swine industry, causing losses of billions of dollars annually. Understanding the immunopathogenesis of the disease is imperative in order to develop strategies to combat this devastating virus. PRRSV infected-SCID pigs failed to develop lesions of PRRSV infection, demonstrating the significant role of the adaptive immunity to PRRSV infection. Finally, we describe the preliminary results of the adoptive transfer of purified CD3⁺ T lymphocytes to SCID pigs from SLA-II matched wild-type littermates, with the objective of establishing a porcine model for the study of T cell immunopathogenesis with viral diseases

Preliminary findings of a previously unrecognized porcine primary immunodeficiency disorder

Weaned pigs from a line bred for increased feed efficiency were enrolled in a study of the role of host genes in the response to infection with Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). However, 4 of the pigs were euthanized early in the study due to weight loss with poor body condition and illness; 2 pigs, before PRRSV infection, and the other 2, approximately 2 weeks after virus inoculation. The 2 inoculated pigs failed to produce PRRSV-specific antibodies. Gross findings included pneumonia, absence of a detectable thymus, and small secondary lymphoid tissues. Histologically, lymph nodes, spleen, tonsils, and Peyer’s patches were sparsely cellular with decreased to absent T and B lymphocytes