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Location: Infectious Bacterial Diseases Research

Title: Increased TNF-alpha/IFN-gamma/IL-2 and decreased TNF-alpha/IFN-gamma production by central memory T cells are associated with protective responses against bovine tuberculosis following BCG vaccination

item Maggioli, Mayara - Iowa State University
item Palmer, Mitchell
item Thacker, Tyler
item Vordermeier, H - Animal & Plant Health Agency Apha
item Mcgill, Jodi - Kansas State University
item Whelan, Adam - Animal & Plant Health Agency Apha
item Larsen, Michelle - Albert Einstein College Of Medicine
item Waters, Wade

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/27/2016
Publication Date: 10/17/2016
Citation: Maggioli, M.F., Palmer, M.V., Thacker, T.C., Vordermeier, H.M., McGill, J.L., Whelan, A.O., Larsen, M.H., Waters, W.R. 2016. Increased TNF-alpha/IFN-gamma/IL-2 and decreased TNF-alpha/IFN-gamma production by central memory T cells are associated with protective responses against bovine tuberculosis following BCG vaccination. Frontiers in Immunology. 7:421.

Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, recent outbreaks of tuberculosis in Texas, Indiana, Nebraska, California, and Colorado as well as recurrence of infection in Michigan demonstrate that the disease is far from eliminated from the United States. Improved techniques are needed for detection of infected cattle as well as improved control strategies (e.g., vaccines). To develop improved tests and vaccines, it is beneficial to first understand the nature of bovine immune responses to the pathogen. In this study, important cell types of cattle involved in memory immune responses to bovine tuberculosis were characterized. In addition, specific mediators of vaccine-evoked protection as well as pathogen-induced inflammation were identified. This basic information will be useful for development of improved tests and vaccines for the control of tuberculosis in cattle.

Technical Abstract: Central memory T cells (Tcm’s) and polyfunctional CD4 T responses contribute to vaccine-elicited protection with both human and bovine tuberculosis (TB); however, their combined role in protective immunity to TB is unclear. To address this question, we evaluated polyfunctional cytokine responses by CD4 T cell effector / memory populations from bacille Calmette Guerin (BCG) vaccinated and non-vaccinated calves prior to and after aerosol challenge with virulent Mycobacterium bovis. Polyfunctional profiles in the response by Tcm’s, effector memory (Tem’s), and effector T cell subsets were similar between BCG-vaccinated and M. bovis-infected calves, only differing in magnitude (i.e., vaccinated < infected). BCG vaccination, however, did alter the kinetics of the ensuing response to aerosol challenge with virulent M. bovis. Early after challenge (3 WPI), non-vaccinates had greater antigen-specific IFN-'/TNF-a and lesser IFN-'/TNF-a/IL-2 responses by Tcm’s than did vaccinated animals. Importantly, differences in responses were also associated with mycobacterial burden upon necropsy. Polyfunctional responses to ESAT-6:CFP10 (antigens not synthesized by BCG strains) were detected in effector, Tem and Tcm populations from BCG vaccinates early after challenge, consistent with the theory that memory and effector T cells expand concurrently during the effector phase of the response and relatively early upon infection. Thus, robust IFN-'/TNF-a responses by Tcm’s are associated with greater mycobacterial burden while IFN-'/TNF-a/IL-2 responses by Tcm’s are indicative of a protective response.