Depletion of CD4(+) and CD8(high+) T-cells before the onset of viraemia during classical swine fever

Leukopenia, in particular lymphopenia, is a characteristic early event duri ng classical swine fever (CSF). This was the case in both highly virulent ( CSF virus (CSFV) strain Brescia) and moderately virulent (CSFV Uelzen) infe ctions. The leukopenia involved leukocyte sub-populations in a disparate ma nner, with B-lymphocytes, helper T-cells and cytotoxic T-cells being the mo st affected. Depletion of lymphocyte sub-populations occurred 1-4 days befo re virus could be detected by RT-PCR in the serum. With the virulent Bresci a virus, depletion was evident by 2 days post-infection (p.i.) but not unti l 3 days p.i. with an equivalent dose of the low virulent Uelzen strain. A lower (1000-fold) dose of the latter virus delayed these kinetics. gamma de lta -TCR+ T-cells were also reduced, but more so with the virulent Brescia infection. The final level of B-and alpha beta -T-cell lymphopenia was simi lar for all animals, including those infected with the lower virus dose. An nexinV staining revealed that cell viability was clearly diminished, partic ularly interesting, considering the clinical differences between infections by Brescia and Uelzen viruses. It was the time p.i. and rate of appearance of dying cells which was more rapid in the virulent Brescia infections. In terestingly the repeated blood sampling resulted in depletion of some leuko cyte populations also in non-infected control animals. Particularly neutrop hils and NK cells, and to a lower extent CD4(+), CD8(+) T-lymphocytes and B -lymphocytes were affected. Taken together, the data show that the alpha be ta -T-lymphocyte subsets are particularly susceptible to modulation during the acute phase of CSF being detectable before the onset of viraemia. The p athogenic mechanism therein would involve indirect virus-host interactions, probably originating from the site of primary infection, rather than a dir ect effect of the virus or viral protein. Furthermore, these characteristic s offer an explanation for the retardation of the cellular and humoral immu ne response observed during classical swine fever. (C) 2001 Elsevier Scienc e B.V. All rights reserved.