Flow cytometric analysis of lymphocyte subset kinetics in Bali cattle experimentally infected with Jembrana disease virus

Abstract

Jembrana disease virus (JDV) is an unusual bovine lentivirus that causes an acute and sometimes fatal disease after a short incubation period in Bali cattle (Bos javanicus). The pathological changes occur primarily in lymphoid tissues, which feature proliferating lymphoblastoid-like cells predominantly throughout parafollicular (T-cell) areas, and atrophy of follicles (B-cell) areas. Five Bali cattle were experimentally infected with JDV and all developed typical clinical signs of Jembrana disease characterised by a transient febrile response, enlargement of superficial lymph nodes and a significant leukopenia. Flow cytometric analysis of PBMC during the acute (febrile) disease phase showed that the reduced number of lymphocytes was due to a significant decrease in both the proportion and absolute numbers of CD4+ T cells, but not CD8+ T-cells or CD21+ B-cells. At the end of the febrile phase, total numbers of both CD8+ T-cells and CD21+ B-cells increased significantly, while CD4+ T-cell numbers remained below normal values, resulting in a significantly reduced CD4+:CD8+ ratio. We speculate that the persistent depletion of CD4+ T cells following JDV infection, through lack of CD4+ T cell help to B cells, may explain the lack of production of JDV-specific antibodies for several weeks after recovery despite an increase in CD21+ B cell numbers. Further, our previous data showing that IgG+ plasma cells are targets for JDV infection, correlated with our current data demonstrating an increase in CD8+ T cell numbers, supports the suggestion that anti-viral cytotoxic T cell or other cell-mediated immune responses may be critical in the recovery process, although this remains to be formally demonstrated for JDV.