Publications

Cell-mediated immunity and CD4(+) cells in particular are important for the resolution of acute infection with non-cytopathic bovine viral diarrhoea virus (BVDV). CD4(+) T cells were shown to recognise virus-infected and non-infectious-protein-pulsed APCs, whereas CD8(+) T cells recognised only virus-infected APCs. T cell recognition was strain cross-reactive and MHC-restricted. Using native and recombinant antigens, we identified the structural glycoprotein E2 and the non-structural protein NS3 as dominant CD4(+) T cell determinants. The repertoire of CD4(+) T cell responses to E2 and NS3 was examined using inbred, homozygous cattle and overlapping synthetic peptides. The repertoire was biased toward conserved regions of NS3 and excluded the hypervariable regions of E2. The number of peptides that were recognised varied between animals but patterns could be distinguished in those animals that shared the same DRB3(*) allele. Of particular interest were: (i) a determinant that was recognised in the context of both DRB3(*) alleles (i.e. DRB3(*)2002 and DRB3(*)0701), (ii) two determinants that were juxtaposed to B cell sites, and (iii) a determinant that had structural analogy with a NS3 epitope previously described for the closely related hepatitis C virus. The minimum stimulatory sequence of the latter, NS3(397-414), was located to residues NS3(400-410).

Herpesvirus infection in tortoises is largely characterized by the development of respiratory clinical signs. Usually lesions develop in the respiratory, oral pharyngeal, intestinal tract and are accompanied by cutaneous and ocular lesions. In chelonids affected by herpesvirus, systemic-type lesions in organs such as the liver and spleen are commonly observed. In this paper we describe a case of multifocal necrotic hepatitis associated with herpesviruses in an adult female land tortoise of the species Testudo horsfieldii. This article is the first description of a viral hepatitis in Testudo spp. with lesions compatible with herpesvirus infection, with no clinical signs or lesions in the respiratory system, oral cavity or other organs.

Resting dendritic cells (DCs) are resident in most tissues and can be activated by environmental stimuli to mature into potent antigen-presenting cells. One important stimulus for DC activation is infection; DCs can be triggered through receptors that recognize microbial components directly or by contact with infection-induced cytokines. We show here that murine DCs undergo phenotypic maturation upon exposure to type I interferons (type I IFNs) in vivo or in vitro. Moreover, DCs either derived from bone marrow cells in vitro or isolated from the spleens of normal animals express IFN-alpha and IFN-beta, suggesting that type I IFNs can act in an autocrine manner to activate DCs. Consistent with this idea, the ability to respond to type I IFN was required for the generation of fully activated DCs from bone marrow precursors, as DCs derived from the bone marrow of mice lacking a functional receptor for type I IFN had reduced expression of costimulatory and adhesion molecules and a diminished ability to stimulate naive T-cell proliferation compared with DCs derived from control bone marrow. Furthermore, the addition of neutralizing anti-IFN-alpha/beta antibody to purified splenic DCs in vitro partially blocked the "spontaneous" activation of these cells, inhibiting the upregulation of costimulatory molecules, secretion of IFN-gamma, and T-cell stimulatory activity. These results show that DCs both secrete and respond to type I IFN, identifying type I interferons as autocrine DC activators.

A comparison of the longitudinal cytokine responses of cattle to infection with intracellular Mycobacterium bovis and extracellular Onchocerca ochengi illustrates the development of reciprocal interferon-? and interleukin-4 responses, which result ultimately in an infection-induced type-1 or type-2 polarization, respectively. These kinetic studies of natural host–pathogen relationships show that the cytokine responses to infection fluctuate over time, resulting in periods of polarization and nonpolarization before the establishment of a chronic infection. Here, we discuss our data from cattle in the light of the current understanding of cytokine polarization towards infection in mouse models and humans.