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Title:   Author  item
                                            Thacker, Tyleritem
                                            Palmer, Mitchellitem
                                            Waters, Wade
  Submitted to: Clinical and Vaccine Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/1/2009
                                    Publication  Date: 8/1/2009
                                    Citation: Thacker, T.C., Palmer, M.V., Waters, W.R. 2009. T-cell mRNA Expression in Response to Mycobacterium bovis BCG Vaccination and Mycobacterium bovis Infection of White-tailed deer. Clinical and Vaccine Immunology. 16(8):1139-1145.Interpretive Summary: Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis in domestic livestock. The cause for many faltering eradication programs is the presence of wildlife reservoirs of M. bovis. One approach in dealing with this wildlife reservoir is to vaccinate deer in order to interrupt transmission. Understanding the immune response to vaccination and infection may be critical to developing more effective vaccines. White-tailed deer were vaccinated with one of two different TB vaccines (BCG Pasteur and BCG Danish). After vaccination, deer were inoculated with virulent M. bovis. At different time points during the experiment the immune system was tested for responses to M. bovis. Immune responses were more closely related to the severity of disease than to vaccination. This information will be useful to agricultural and wildlife officials as well as USDA action agencies such as APHIS.
                                Technical Abstract: Understanding immune responses of white-tailed deer (WTD) to infection with Mycobacterium bovis provides insight into mechanisms of pathogen control and may provide clues to development of effective vaccine strategies. WTD were vaccinated with either BCG strain Pasteur or BCG Danish. Both vaccinates and unvaccinated controls were infected with virulent M. bovis. At various time points PBMC were isolated and stimulated in vitro and gene expression measured by Real-time RT PCR. T cell responses were measured by assessing the relative expression of IFN-gamma, Tbet, IL-12p40, IL-12p35, IL-23p19, FoxP3, IL-17 and GATA3. After vaccination, animals vaccinated with BCG Danish expressed significantly more TH1 cytokines than either BCG Pasteur or unvaccinated controls. BCG Pasteur vaccinated animals expressed more GATA3 than either group. After infection unvaccinated controls expressed more Tbet and IL-12p40 than vaccinated animals. BCG Pasteur vaccinated animals expressed more GATA3 than either the unvaccinated controls or the BCG Danish vaccinated animals after infection. Animals were divided into pathology groups irrespective of vaccine status to correlate gene expression with severity of pathology. Animals in the high pathology group expressed more Tbet and IFN-gamma than animals with no pathology, while low pathology animal expression was intermediate. The high pathology group expressed less GATA3 than did the no pathology group with low pathology group being intermediate, thus correlating inversely with pathology. Gene expression correlated more closely with pathology group than vaccination group.


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