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ABSTRACT- The mononuclear cell infiltrate in the liver was analyzed, using a panel of monoclonal antibodies (MAbs) of known specificity, in 10 patients with auto-immune chronic active hepatitis and, for contrast, in 14 with other types of chronic parenchymal liver diseases. In all cases, the mononuclear cell (MNC) infiltrate in the liver consisted mostly of T lymphocytes. Helper (Th) cells were more frequent than suppressor/cytotoxic T cells (Tsc) in the portal tracts and cirrhotic scar tissue, while Tsc were more common in the hepatic parenchyma. The number of Tsc cells in the parenchyma was greatest in patients with histologically active CAH and least in patients with quiescent cirrhosis. 'Plasmacytoid' cells with the morphology of plasma cells, a hallmark of the MNC infiltrate in auto-immune CAH, were more frequent in histologically active CAH than in quiescent cirrhosis. These plasmacytoid cells were T200 + ve, and hence of bone marrow origin, but the majority expressed neither membrane nor cytoplasmic immunoglobulin nor any lineage-specific marker antigens, and hence did not fulfil criteria for B lymphocytes; however, these cells were positive for OKT10 and HLA DR. No difference was evident between the MNC infiltrate in the liver in auto-immune CAH and that in the other acute or chronic liver diseases studied, including HBV-associated CAH; hence immunohistological studies do not point to any pathological processes uniquely responsible for the pattern of hepatocyte damage seen in auto-immune CAH. [ABSTRACT FROM AUTHOR]

We measured two ectoenzymes, ecto-5 ′-nucleotidase (NT) and dipeptidyl peptidase IV (DP) in the peripheral blood lymphocytes of various groups of HIV-infected patients because of the previous implied relationship of these enzymes to immune function. NT expressed as mean nmol/h per mg protein (±s.d.) was significantly depressed in the HIV-seropositive asymptomatic (42 ± 32; P <0.01) and AIDS groups (14 ± 7; P <0.002) when compared with a healthy HIV-seronegative male population (83 ± 27). The NT activities in asymptomatic HIV-seropositive and HIV-seronegative high risk groups (53 ± 30) were not significantly different from one another but both groups had significantly higher enzyme activities than the AIDS group (P = 0.01 and <0.002, respectively). The seronegative high risk and normal healthy group had similar NT activities. DP activities expressed as mean nmol/h per mg protein (± s.d.) in both seropositive asymptomatic (0.188 ± 0.038) and high risk seronegative (0.180 ± 0.05) groups had higher enzyme activities than the healthy seronegative (0.117 ± 0.015; P = 0.02 and 0.05, respectively) and A1DS group (0.096 ± 0.036; P = 0.002 and 0.02, respectively). The healthy seronegative group had DP activities not significantly different to the AIDS groups. Similarly the high risk seronegative and healthy seropositive group had similar DP activities. These results taken together indicate that measurement of both DP and NT should be evaluated prospectively as a monitor of the clinical progression of HIV infection. [ABSTRACT FROM AUTHOR]

Virus-like particles (VLPs) are being currently investigated in vaccines against viral infections in humans. There are different recombinant-protein-expression systems available for obtaining the necessary VLP preparation for vaccination. However, the differences in post-translational modifications of the recombinant proteins obtained and their differences in efficacy in eliciting an anti-viral response in vaccines are not well established. In this study we have compared the post-translational modifications of human papillomavirus type-6b major capsid protein L1 (HPV 6bL1) expressed using recombinant baculovirus (rBV) in Sf9 (Spodoptera frugiperda) insect cells, with the protein expressed using recombinant vaccinia virus (rVV) in CV-1 kidney epithelial cells. Two-dimensional gel electrophoresis of biosynthetically labelled rBV-expressed HPV 6bL1 showed several post-translationally modified variants of the protein, whereas rVV-expressed HPV 6bL1 showed only a few variants. Phosphorylations were detected at threonine and serine residues for the L1 expressed from rBV compared with phosphorylation at serine residues only for the L1 expressed from rVV. HPV 6bL1 expressed using rBV incorporated [(3)H]mannose and [(3)H]galactose, whereas HPV 6bL1 expressed using rVV incorporated only [(3)H]galactose. We conclude that post-translational modification of recombinant HPV 6bL1 can differ according to the system used for its expression. Since recombinant L1 protein is a potential human-vaccine candidate, the implication of the observed differences in post-translational modifications on immunogenicity of L1 VLPs warrants investigation.

There is substantial evidence from experiments of nature that immune competence plays a major part in determining the outcome of anogenital human papillomavirus (HPV) infection. Cellular rather than humoral immunity would appear to be the key to the control and eradication of HPV-induced warts. It seems likely that the HPV early proteins, which are responsible for viral replication (E1 and E2) and for promoting tissue proliferation (E6 and E7) will be the target antigens recognized by antigen-specific T cells. Natural infection is slow to produce an appropriate therapeutic immune response to these proteins, probably because HPV has adopted a strategy to prevent the effective presentation of viral antigens to the host immune system. Human papillomavirus infection is non-lytic so there is little release of viral antigen to professional antigen-presenting cells. Additionally no local proinflammatory cytokine production and no local inflammation is induced by HPV infection. An optimal therapeutic strategy for anogenital HPV infection would be, therefore, to accelerate the induction of a strong virus-specific immune response by inducing local inflammation and the cytokines necessary to invoke HPV-specific immunity.

A subgroup of human papillomaviruses (HPVs) is implicated in the aetiology of neoplastic change in anogenital epithelium. Although abundant circumstantial evidence exists for the involvement of the immune system in the control of HPV infection, restriction of infection to epithelium and the lack of a viral productive phase pose problems for immune response induction, and for immunological effector mechanisms. In this article we discuss how HPV antigens may be presented to the immune system on the surface of keratinocytes as well as, or in addition to, presentation by 'classical' antigen presenting cells, and outline putative roles for non-specific and specific (B- and T-cell) effector functions. We discuss the prospects for a vaccine and the use of anti-HPV antibodies in immunodiagnosis.