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

Central memory T cells (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...

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Main Authors: Mayara Fernanda Maggioli, Mitchell Palmer, Tyler C. Thacker, Hans Martin Vordermeier, Jodi L. McGill, Adam O. Whelan, Michelle H. Larsen, William R. Jacobs, W. Ray Waters
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00421/full
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author Mayara Fernanda Maggioli
Mayara Fernanda Maggioli
Mitchell Palmer
Tyler C. Thacker
Hans Martin Vordermeier
Jodi L. McGill
Adam O. Whelan
Michelle H. Larsen
William R. Jacobs
W. Ray Waters
author_facet Mayara Fernanda Maggioli
Mayara Fernanda Maggioli
Mitchell Palmer
Tyler C. Thacker
Hans Martin Vordermeier
Jodi L. McGill
Adam O. Whelan
Michelle H. Larsen
William R. Jacobs
W. Ray Waters
author_sort Mayara Fernanda Maggioli
collection DOAJ
description Central memory T cells (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 prior to and after aerosol challenge with virulent Mycobacterium bovis. Polyfunctional cytokine expression patterns in the response by Tcm, effector memory, and effector T cell subsets were similar between BCG-vaccinated and M. bovis-infected calves; only differing in magnitude (i.e., infected > vaccinated). BCG vaccination, however, did alter the kinetics of the ensuing response to virulent M. bovis infection. Early after challenge (three weeks post-infection), non-vaccinates had greater antigen-specific IFN-γ/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 three 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.
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spelling doaj.art-0cfc4e0e1c164fda81e7c8f9389a2c042022-12-21T20:39:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-10-01710.3389/fimmu.2016.00421215084Increased 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 vaccinationMayara Fernanda Maggioli0Mayara Fernanda Maggioli1Mitchell Palmer2Tyler C. Thacker3Hans Martin Vordermeier4Jodi L. McGill5Adam O. Whelan6Michelle H. Larsen7William R. Jacobs8W. Ray Waters9National Animal Disease CenterCollege of Veterinary Medicine, Iowa State UniversityNational Animal Disease CenterNational Animal Disease CenterAnimal and Plant Health Agency—WeybridgeCollege of Veterinary Medicine, Kansas State UniversityDefense Science and Technology LaboratoryAlbert Einstein College of MedicineAlbert Einstein College of MedicineNational Animal Disease CenterCentral memory T cells (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 prior to and after aerosol challenge with virulent Mycobacterium bovis. Polyfunctional cytokine expression patterns in the response by Tcm, effector memory, and effector T cell subsets were similar between BCG-vaccinated and M. bovis-infected calves; only differing in magnitude (i.e., infected > vaccinated). BCG vaccination, however, did alter the kinetics of the ensuing response to virulent M. bovis infection. Early after challenge (three weeks post-infection), non-vaccinates had greater antigen-specific IFN-γ/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 three 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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00421/fullBCG Vaccinepolyfunctional T cellsbovine tuberculosisCentral memory T cellscalf model
spellingShingle Mayara Fernanda Maggioli
Mayara Fernanda Maggioli
Mitchell Palmer
Tyler C. Thacker
Hans Martin Vordermeier
Jodi L. McGill
Adam O. Whelan
Michelle H. Larsen
William R. Jacobs
W. Ray Waters
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
BCG Vaccine
polyfunctional T cells
bovine tuberculosis
Central memory T cells
calf model
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic BCG Vaccine
polyfunctional T cells
bovine tuberculosis
Central memory T cells
calf model
url http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00421/full
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