infection in HIV-positive subjects: a retrospective analysis of 24 cases

infection in HIV-positive subjects: a retrospective analysis of 24 cases. also had a trend toward higher IgGT association compared to the isotype association of antibody in adult horses and healthy exposed foals. This suggests that in horses, IgGb and IgGT are Th2 isotypes and IgGa is a Th1 isotype. Furthermore, it suggests that foals which develop pneumonia have a Th2-biased, ineffective immune response whereas foals which become immune develop a Th1-biased immune response. Pneumonic foals had significantly more antibody to VapD and VapE than did healthy exposed foals. This may indicate a difference in the expression of these two Vap proteins during persistent infection. Alternatively, in pneumonic foals the deviation of the immune response toward VapD Econazole nitrate and VapE may reflect a bias unfavorable to resistance. These data indicate possible age-related differences in the equine immune response affecting Th1-Th2 bias as well as antibody specificity bias, which together favor the susceptibility of foals to pneumonia. causes pyogranulomatous bronchopneumonia in foals younger than 4 months and induces significant economic losses on endemically infected horse-breeding farms (29). This gram-positive, facultatively intracellular bacterium is an opportunistic pathogen in immunocompromised humans, such as those infected with human immunodeficiency virus (2, 9, 13). Foal-virulent strains possess an 81-kb plasmid and express VapA, a plasmid-encoded, surface-expressed lipoprotein (38, 40-,42). VapA is a member of a family of seven Vap proteins (VapA and VapC to VapH), which have homology in their C-terminal halves and are encoded within a 27-kb pathogenicity island on the large plasmid (37). The function of these proteins is not known. Protection of foals against appears to rely on cooperation and interdependency between the antibody-mediated and cell-mediated immune response. Antibody appears to contribute to protection since the period of maximum susceptibility coincides with declining levels of maternally derived antibody (29). Econazole nitrate In addition, antibody opsonizes for uptake and killing by macrophages and neutrophils in vitro (45, 47, 48) and may facilitate the killing of in vivo. Vap-specific antibodies protect immunosuppressed mice since purified immunoglobulin G (IgG) from APTX (a VapA-enriched antigen)-vaccinated horses protected against intraperitoneal challenge with whereas nonimmune equine IgG failed to protect (10). Pulmonary clearance of virulent in mice requires functional T lymphocytes (3, 46). Both CD4+ and CD8+ T cells apparently contribute to protection (26, 33), and CD4+ cells are necessary for complete pulmonary clearance of in mice (16). Mice in which a Th2 cytokine response was induced by administration of monoclonal antibodies against gamma interferon (IFN-) prior to experimental infection with virulent failed to clear the bacteria and developed pulmonary granulomas (17). In contrast, immunocompetent BALB/c mice developed a Th1 cytokine response and cleared the infection (17). Adoptive transfer of (18). Virulent can modulate the cytokine response in foals, down-regulating IFN- mRNA expression in CD4+ T cells and up-regulating lung interleukin-10 expression (12). These cytokines may influence the Th1-Th2 balance of the immune response in foals. Although antibody provides partial protection against pneumonia (14), the role of the Ig isotype has not been described. Prescott et al. determined that the antibody response of young foals to the APTX antigen with aluminium hydroxide adjuvant induced a KDM5C antibody more IgGb- and IgGT-biased subisotype response than did natural infection, which induced an IgGa-dominant response (30). Vaccination with this antigen and adjuvant exacerbated disease in the foals after natural challenge with (30). An aluminium hydroxide-based influenza vaccine also induced an IgGT-biased response in horses, with some evidence of an IgGc response. These vaccinated horses were not resistant to infection even though they had an anamnestic IgGT response (25). In contrast, natural infection with influenza virus induced virus-specific IgGa and IgGb (25). In mice and humans, the antibody isotype reflects the Th1-Th2 bias of the immune response. A similar bias may occur in horses. The IgG subisotype profile of the antibody response associated with protective immunity to infection has not been described. The study reported here addresses the hypothesis that resistance or susceptibility to pneumonia in foals is associated with distinct IgG subisotype-related antibody responses to the seven virulence-related Vap proteins and that in pneumonic foals the profile reflects a Th2-biased response whereas in healthy foals and adults the profile reflects a Th1-biased response. MATERIALS AND METHODS Experimental design. Serum was collected biweekly from clinically normal pony foals (= 6) kept on pasture at a University of Guelph research farm that had a history of infections in foals. The serum sample in which the peak antibody response to VapA was observed over the first 6 months of a foal’s life was used to determine the isotype profile of the anti-Vap response compared to sera obtained from a group of clinically normal, unrelated Econazole nitrate adult horses (= 6) at the same farm and from a third group of foals with clinical pneumonia (= 8). The clinical case samples were obtained from client animals at the University of Florida and the.