Overview of the Third International Workshop on Swine Leukocyte Differentiation Antigens.

The aim of the Third International Workshop on Swine Leukocyte Differentiation Antigens (CD workshop), supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS), was to standardize the assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte differentiation antigens and to define new antibody clusters, using nomenclature in accordance with human and ruminant CD nomenclature, as agreed at the summary meeting of the Second International Swine CD Workshop in Davis, 1995: only mAb with proven reactivity for the orthologous porcine gene product or cross-reactivity for the human gene products, were given the full CD nomenclature, all other allocations were prefixed with "w". As in previous workshops, the overall organization was entrusted to the chair and first author, with support by the chair of the previous workshop and second author. In addition to the existing 26 pig leukocyte CD/SWC determinants established in previous workshops, this workshop established/confirmed another 11 CDs for pig leukocytes, identified by a total of 21 mAb: CD11R1 (2 mAb), CD11R2 (1 mAb), CD11R3 (4 mAb), wCD40 (1 mAb), wCD46 (4 mAb), wCD47 (3 mAb), wCD49d (1 mAb), CD61 (1 mAb), wCD92 (1 mAb), wCD93 (1 mAb) and CD163 (2 mAb).

Summary of the first round analyses of the Third International Workshop on Swine Leukocyte Differentiation Antigens.

The reactivity of 155 monoclonal antibodies submitted to the Third International Workshop on Swine Leukocyte Differentiation Antigens, together with 41 internal standards, was analysed by flow cytometry on 29 different pig cell targets as well as two human cell targets as a means of establishing suitable panels of monoclonal antibodies for more detailed clustering analyses by the various subsections of the workshop. Results were collected either without further gating, with gating based on FS/SS characteristics or with gating based on the co-expression of a reference antibody in two-colour flow cytometry. The CD or SWC reactivity of the internal standards had been established in previous workshops. Data sets were subsequently analysed by statistical clustering using the Leucocyte Typing Database IV software. The resulting 18 cluster groups were allocated to the appropriate second round sections of the workshop, after reviewing the overall cellular reactivity of each cluster as well as the specificity of known standards which clustered in a group.

Differences among HIV-1 variants in their ability to elicit secretion of TNF-alpha.

HIV-1 infection of human PBMC has been shown to elicit secretion of several different cytokines. TNF-alpha secretion induced by this virus has been of particular interest because it has been associated with the development of HIV-1 dementia and because TNF-alpha increases viral replication by enhancing NF-kappaB interaction with the viral promoter, the HIV-1 long terminal repeat. Thus, an autocrine pathway is potentially created in which HIV-1 stimulates its own replication. Conflicting reports exist, however, on the ability of HIV-1 to induce TNF-alpha secretion in vitro or in vivo. Using experimental protocols that controlled for potential bacterial endotoxin-induced TNF-alpha secretion, the current study demonstrates significant differences in TNF-alpha-eliciting properties among primary and laboratory obtained HIV-1. The relative TNF-alpha-inducing ability of different variants is conserved when tested using PBMC from different individuals. Elicitation of TNF-alpha secretion was not blocked by exposure of cells to zidovudine, indicating that viral integration was not required to induce secretion. Rather, the interaction between the virus and cell surface is critical for TNF-alpha induction, as Abs against CD4 or CCR5 blocked the induction of TNF-alpha synthesis by PBMC when added before virus exposure. Furthermore, the ability to induce TNF-alpha secretion mapped to a region of the HIV-1 env gene that includes the third hypervariable domain. Differences in the ability of different HIV-1 variants to elicit TNF-alpha may account for individual differences in HIV-1 disease course.

A perspective on cellular immunity in the elderly.

The increased incidence of infection and malignancy in elderly individuals has prompted many studies that demonstrate that the aging immune system is impaired. Most of these studies have focused on the impairment of acquired immunity provided by lymphocytes. While defects in acquired humoral and T-cell-mediated immunity may exist, increased susceptibility to infection may result from defects in the constitutive functioning of macrophages and granulocytes. Recognition of the potential importance of defects in constitutive immunity in the elderly may provide new opportunities for therapeutic and prophylactic intervention in this population.

Opiates and infection.

This review on the effects of opiate use on infectious diseases discusses the complete spectrum of infections in the opiate user, including those of the lung, the GI tract, the skin, the skeletal system, and the CNS. There is both increased prevalence and increased severity of bacterial and viral infections in injection drug users with the outcome of increased morbidity and mortality. The experimental administration of opiates has lead to a greater understanding of the effects on susceptibility to and progression of infectious diseases. Animal models of opiate dependence and infection are reviewed with specific attention to cases in which the opiate-mediated effects are harmful and in which cases they are beneficial.

Infection of swine with Mycobacterium bovis as a model of human tuberculosis.

Swine were infected with Mycobacterium bovis to develop a model for pulmonary and disseminated tuberculosis in humans. Pigs were inoculated with various doses of M. bovis by intravenous (i.v.), intratracheal (int), or tonsillar routes. Animals were euthanized between 17 and 60 days after inoculation, and tissues were collected for culture and histopathologic examination. Lesions of disseminated tuberculosis were found in pigs given 10(4) or 10(8) cfu of M. bovis i.v. or int; localized pulmonary disease was found in pigs given 10(2) or 10(3) cfu of M. bovis int. Lesions ranged from well-organized tubercles with coagulative necrosis, epithelioid macrophages, and fibrosis to large expansive tubercles with liquefactive necrosis and extracellular growth of M. bovis. Tuberculous meningitis was observed in animals given M. bovis i.v. Swine infected with M. bovis are a useful animal model for elucidating the mechanisms of pathogenesis and host defense to tuberculosis in humans.

Differential infection of porcine alveolar macrophage subpopulations by nonopsonized Mycobacterium bovis involves CD14 receptors.

The resurgence in mycobacterial infection worldwide has led to renewed attention to the pathogenesis of Mycobacterium species. The purpose of this study was to characterize the infection of alveolar macrophages (AMs) by nonopsonized Mycobacterium bovis, and to elucidate the mechanism by which a differential infection of subpopulations of AM may occur. A difference in susceptibility to Mycobacterium bovis infection of subpopulations of AMs was observed, such that the least dense cells were the least susceptible (21.4 +/- 10.7%) and the most dense cells were the most readily infected (61.8 +/- 5.6%). The percentage of AMs staining for CD14 receptors showed a similar differential distribution, with fewer of the least dense cells expressing CD14 and a greater percentage of the most dense cells staining for CD14 receptor expression. To investigate the role of CD14 receptors in the infection of AMs, anti-CD14 antibody was added to the cell cultures. Infection of AM by Mycobacterium bovis was blocked by up to 60.2% by anti-CD14 antibody but not by isotype control antibody. The results of this study suggest that Mycobacterium bovis selectively infects AM subpopulations, specifically those with the greatest expression of CD14, a putative receptor mechanism for Mycobacterium bovis infection of porcine AM.

Cytokine and free radical production by porcine microglia.

Swine have been used increasingly as an animal model for a variety of immunologic purposes. Because the functional activities of porcine microglia, the resident macrophages of the brain, have not been elucidated, highly enriched porcine microglial cell cultures were developed in the present study to assess cytokine and free radical production by these cells compared to microglia of human and murine origin. Porcine microglial cells were found to behave similarly to both human and murine cells in releasing tumor necrosis factor-alpha and interleukin-1 and in generating superoxide anion. In contrast to murine cells, porcine microglial cells, like human cells, failed to generate NO in response to cytokine stimulation. These findings suggest that swine will serve as an excellent model for investigations of central nervous system diseases in which microglia are involved in host defense or neuronal injury.