Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/15/2002
Publication Date: 11/20/2002
Citation: Naiman, B., Blumerman, S., Alt, D.P., Bolin, C., Brown, R., Zuerner, R.L., Baldwin, C. 2002. Evaluation of type 1 immune response in naive and vaccinated animals following challenge with leptospira borgpetersenii serovar hardjo: involvement of wc1**+ gamma delta and cd4 t cells. Infection and Immunity. 70(11)6147-57. Interpretive Summary: Infection in cattle with Leptospira borgpetersenii serovar hardjo occurs throughout the world, causing abortion as well as being shed in urine, providing sources of infection for humans. Immunity in vaccinated cattle was recently shown to be associated with induction of a type 1 (TH1) cell-mediated immune response. Here, naive and vaccinated pregnant cattle were challenged with serovar hardjo and their immune responses were studied. Clear differences were seen in the immune responses of the cattle after challenge. Assays measuring cellular proliferation and interferon-gamma production were consistent throughout the study with production of a TH1 immune response in vaccinated cattle. Certain cell types were identified among those responding in the vaccinated animals and these cells are likely to be important in protection from infection. While naive and vaccinated animals had similar levels of one class of antibody, vaccinated animals had 1.4 fold more of another antibody class than did nonvaccinates. Nonvaccinated cattle challenged with serovar hardjo did show cellular proliferation at one time point after challenge. Thus, although infection may induce a TH1 immune response in nonvaccinated cattle it fails to prevent establishment of chronic infection.
Technical Abstract: Leptospirosis is an emerging zoonotic disease in humans. Infection in cattle with Leptopira borgpetersenii serovar hardjo occurs throughout the world, causing abortion as well as being shed in urine, providing sources of infection for humans. Sterile immunity in vaccinated cattle was recently shown to be associated with induction of a type 1(Th1) cell-mediated immune response. Here, naïve and vaccinated pregnant cattle were challenged with serovar hardjo and their immune responses were studied. Antigen-induced proliferation of lymphocytes in peripheral blood mononuclear cells (PBMC) were evident throughout the post-challenge period in vaccinated cattle, but at only one of the time points evaluated in naive cattle. Beginning 2 weeks after challenge, interferon-gamma (IFN-g) was measured in supernatants of antigen-stimulated PBMC cultures from nonvaccinated and vaccinated animals. PBMC from nonvaccinated animals always produced less IFN-gamma than PBMC from vaccinated animals. By flow cytometric analysis, IFN-gamma+ cells were evident in vitro in antigen-stimulated cultures of PBMC from vaccinated animals throughout the post-challenge period and shown to be largely CD4+ and WC1+ T cells. Similar proportions of these 2 subpopulations were found among dividing cells in antigen-stimulated cultures. In contrast, with PBMC from naive/challenged animals a substantial proportion of IFN-gamma+ cells were infrequently found in antigen-stimulated cultures and often only when similar percentages were found in medium control cultures suggesting nonspecific responses. Finally, naive and vaccinated animals had similar levels of antigen-specific IgG1 following challenge while vaccinated animals had 1.4 fold more IgG2. Thus, while infection may induce a Th1 response we suggest it fails to prevent establishment of chronic infection.