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This report describes the clinical and pathological findings of a suspected idiosyncratic adverse drug reaction in a young dog. The patient presented with sudden onset, severe skin lesions together with episodes of collapse. Investigations revealed a neutrophilic dermatitis with vasculitis, immune-mediated haemolytic anaemia and thrombocytopenia. Similar pathology has been described in human cases of Sweet's syndrome. The chronology of events suggested an adverse drug reaction to carprofen, although two antibiotics had been prescribed within the dog's recent history. Lymphocyte transformation tests were performed and tended to exclude both antibiotics as the cause of the reaction. To the authors' knowledge, lymphocyte transformation tests have not previously been described with regard to drug hypersensitivity assessment in the veterinary literature, and this is the first peer-reviewed case report of neutrophilic dermatitis and vasculitis with immune-mediated haemolytic anaemia and thrombocytopenia occurring as a suspected adverse drug reaction to carprofen in the dog.

We have isolated a maedi-visna-like virus from the peripheral blood mononuclear cells of a British sheep displaying symptoms of arthritis and pneumonia. After brief passage in fibroblasts this virus (designated EV 1) was used to infect choroid plexus cells, cDNA clones of the virus were prepared from these cells and sequenced. Gaps between non-overlapping clones were filled using gene amplification by the polymerase chain reaction. The genome structure is similar to that described for visna virus strain 1514, and differs from that described for visna virus strain SA-OMVV in not having a W reading frame. Overall the genome differs by about 20 % between each of these strains, but there is fivefold variation in the amount of divergence of derived amino acid sequences of different open reading frames. Two sequenced EV1 clones each contain only one copy of the 43 bp repeat, with paired AP-1 sites, which is a feature of other ruminant lentiviral long terminal repeats (LTRs). However, analysis of viral DNA in infected cells by gene amplification shows that LTRs with two repeats do occur, albeit at a relatively low frequency.

Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium.

SUMMARYMouse L cell lines have been developed which constitutively express glycoproteins B (gB) and D (gD) of herpes simplex virus type 1. When used to study the immune response of mice to the viral glycoproteins, it was found that both gB and gD induce a delayed type hypersensitivity response and both also induce an antibody response, but only the cell line expressing gD could stimulate the production of neutralizing antibody. Virus-specific cytotoxic T lymphocytes (CTLs) recognized gB expressed by the cell line and this line could also induce CTLs in mice. Recognition of gD by major histocompatibility complex class I restricted CTLs was never seen. Vaccination of mice with the cell lines provided protection from viral challenge and inhibited the establishment of a latent infection, although gD proved to be the better protective immunogen. INTRODUCTIONThe immune response of mice to herpes simplex virus type 1 (HSV-1) is known to involve both antibody and cell-mediated protective mechanisms. In particular, T lymphocytes are considered to play a central role in the recovery from a primary infection (for review, see Nash et al., 1985). However, the particular proteins of the virus recognized by these cells are far from clear. Experiments to date have centred on the use of the virus mutants deficient in the expression of certain glycoproteins to study the nature of the antigens recognized by cytotoxic T lymphocytes (CTLs) (Carter et al., 1981;Lawman et al., 1980;Glorioso et al., 1985), and the affinity purification of glycoproteins from whole virus preparations for use as immunogens to study delayed type hypersensitivity (DTH) responses (Schrier et al., 1983;Chan et al., 1985).The main problem has been how to separate the various antigens of this complex virus in order to dissect the nature of the immune response. Our approach has been to investigate the immune response to individual glycoproteins of HSV-1 by expressing the appropriate genes in mouse L cells. In this system, the glycoproteins are expressed in isolation but are still presented at the cell surface analogous to infected cells. Our reason for choosing glycoproteins is that they are likely to represent major target antigens of the immune system: this is true for the antibody response (for review, see Norrild, 1985) and there is evidence to suggest that glycoproteins are the major targets for both major histocompatibility complex (MHC) class I and class II restricted T lymphocytes (Carter et al., 1981 ;Lawman et al., 1980;Glorioso et al., 1985;Schrier et al., 1983).In this paper we report the establishment of L cells expressing either glycoprotein B (gB) or D (gD) and the use of these lines to study the specificity of the T cell response to HSV-1. The lines were also used to immunize mice against primary virus infections and to prevent the establishment of latent infections.