Trypanosoma (Trypanozoon) evansi (Steel, 1885) : immune responses and immunosuppression during experimental infection in sheep

• Main Author: Onah, Denis Nnabuike
• Published: University of Edinburgh 1992
• Subjects: 636.089
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.660207

This thesis describes studies on immune responses and immunosuppression during experimental <i>Trypanosoma evansi</i> infections in sheep. The studies were initiated by investigations into: 1) routine parasitology and haematology, 2) cell population dynamics in blood and, 3) assessment of parasite-specific antibody responses. Investigations into the role of <i>T.evansi</i> in suppression of immune responses to heterologous antigens were carried out using <i>Pasteurella haemolytica</i> vaccine as a model antigen and involved: 1) assessment of local inflammation, and measurement of skin thickness, at the site of vaccination, 2) cell phenotype dynamics in blood and in efferent lymph draining the site of vaccination, 3) assay of anti-<i>Pasteurella</i> antibodies, 4) cellular responses to T and B cell mitogens. <i>Pasteurella</i> and homologous trypanosomal antigens <i>in vitro</i>, 5) cell depletion experiments to try and identify the cell phenotype(s) responsible for immunosuppression. <i>T.evansi</i> infections in sheep produced scanty and frequently cryptic parasitaemia, ending in selfcure in some cases. There was marked lymphocytosis from day 22 post infection (p.i.). Indirect immunofluorescence and flow cytometry revealed decreases in the proportions of CD5<SUP></SUP>+ , CD4<SUP></SUP>+ , CD8<SUP></SUP>+ and SBU-T19<SUP></SUP>+ (γdelta) T cells, which were paralleled by increases in slg<SUP></SUP>+ , CD45R<SUP></SUP>+ , CD1<SUP></SUP>+ cells and cells expressing the MHC Class II antigen. These changes were relatively minor in the selfcured sheep except that there was a greater decrease in CD8<SUP></SUP>+ than CD4<SUP></SUP>+ cells resulting in increased CD4:CD8 ratio. Trypanosome-specific IgG and IgM antibodies were detected in all infected animals by enzyme immunoassays. However, the levels of these antibodies were greater in the selfcured animals. <i>T.evansi</i> infection actively suppressed the local inflammation and skin thickness normally induced in uninfected control sheep by subcutaneous inoculation of <i>Pasteurella</i> vaccine. Moreover, early systemic mobilisation of neutrophils as seen in uninfected controls was suppressed. Analysis of cell dynamics in the blood of infected, vaccinated sheep revealed that vaccination did not reverse the changes in the proportions of T cell subsets and B cells which was induced by <i>T.evansi</i> in the infected sheep. Two-colour cytometry also showed that <i>T.evansi</i> induced increases of up to 70 percent in B cells expressing the CD5 antigen (CD5<SUP></SUP>+ B cells) which persisted after vaccination but was minimal in the selfcured animals.