The role of regulatory T cells during infection with feline infectious peritonitis virus

Feline infectious peritonitis virus (FIPV), a coronavirus with a near 100% fatality in cats, is thought to be controlled by a strong cell-mediated immunity. Regulatory T cells (Tregs), are a subset of lymphocytes that can suppress the mounting immune response during a normal immune reaction by direct interaction with effector T cells and the production of cytokines (IL-10 and TGF-β). Tregs have been implicated in many autoimmune diseases such as multiple sclerosis and Crohn’s disease as well as in many chronic virus infections such as Epstein-Barr virus, herpes simplex virus and both human and feline immunodeficiency virus infections. The typical chronic infection and immunopathogenesis of FIPV suggests that Tregs might not be functioning correctly during infection. In the present study, Tregs were quantified in blood, mesenteric lymph node (mLN), spleen, kidney and mesentery of FIPVinfected cats as well as in control cats. Immunofluorescence staining were performed using monoclonal antibodies against CD3, CD4, CD8, CD25 and Foxp3 to detect regulatory cells. Flow cytometrical analysis revealed that classical Tregs (CD4+CD25+Foxp3+) were drastically depleted from the blood, mLN and spleen in FIP cats when compared to healthy cats. Additionally, other regulatory T cells (CD4+CD25-Foxp3+ and CD3+CD8+Foxp3+) were also found to be depleted from the immunological compartments. Inflamed tissue however, did not shown any differences in Treg numbers. These results indicate that during a FIPV infection, the number of Foxp3 regulatory cells is drastically lowered in the blood, mLN and spleen. This reduction was not due to migration to lymphoid organs nor to sites of infection and will contribute substantially to the unchecked overwhelming immune response and inflammatory state that follows FIPV infection and eventually causes the death of infected cats. Additional Treg functionality assays will further elucidate the role of Tregs in the immunopathology of FIPV infection and determine if Tregs can be of therapeutic use