title: Increased TNF-α/IFN-γ/IL-2 and Decreased TNF-α/IFN-γ Production by Central Memory T Cells Are Associated with Protective Responses against Bovine Tuberculosis Following BCG Vaccination.
abstract: Central memory T cell (Tcm) and polyfunctional CD4 T cell 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 by flow cytometry prior to and after aerosol challenge with virulentMycobacterium bovis. Polyfunctional cytokine expression patterns in the response by Tcm, effector memory, and effector T cell subsets were similar between BCG-vaccinated andM. bovis-infected calves, only differing in magnitude (i.e., infected > vaccinated). BCG vaccination, however, did alter the kinetics of the ensuing response to virulentM. bovisinfection. Early after challenge (3 weeks post-infection), non-vaccinates had greater antigen-specific interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α) and lesser IFN-γ/TNF-α/IL-2 responses by Tcm cells than did vaccinated animals. Importantly, these differences were also associated with mycobacterial burden upon necropsy. Polyfunctional responses to ESAT-6:CFP10 (antigens not synthesized by BCG strains) were detected in memory subsets, as well as in effector cells, as early as 3 weeks after challenge. These findings suggest that cell fate divergence may occur early after antigen priming in the response to bovine TB and that memory and effector T cells may expand concurrently during the initial phase of the immune response. In summary, robust IFN-γ/TNF-α response by Tcm cells is associated with greater mycobacterial burden, while IFN-γ/TNF-α/IL-2 response by Tcm cells are indicative of a protective response to bovine TB.
authors: Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, Ames, IA, USA; Imbio, Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors: Mayara F
authors: MF
authors: Maggioli
authors: Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center , Ames, IA , USA.
authors: Mitchell V
authors: MV
authors: Palmer
authors: Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center , Ames, IA , USA.
authors: Tyler C
authors: TC
authors: Thacker
authors: Tuberculosis Research Group, Animal and Plant Health Agency , Addlestone , UK.
authors: Hans Martin
authors: HM
authors: Vordermeier
authors: Department of Diagnostic Medicine and Pathology, College of Veterinary Medicine, Kansas State University , Manhattan, KS , USA.
authors: Jodi L
authors: JL
authors: McGill
authors: Defense Science and Technology Laboratory, Porton Down , Wiltshire , UK.
authors: Adam O
authors: AO
authors: Whelan
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine , Bronx, NY , USA.
authors: Michelle H
authors: MH
authors: Larsen
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine , Bronx, NY , USA.
authors: William R
authors: WR
authors: Jacobs
authors: Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center , Ames, IA , USA.
authors: W Ray
authors: WR
authors: Waters
keywords: bovine tuberculosis; calf model; central memory T cells; polyfunctional T cells