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...
Main Authors: | , , , , , , , , |
---|---|
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 |
_version_ | 1818834757259100160 |
---|---|
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. |
first_indexed | 2024-12-19T02:39:53Z |
format | Article |
id | doaj.art-0cfc4e0e1c164fda81e7c8f9389a2c04 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-12-19T02:39:53Z |
publishDate | 2016-10-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
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 |
work_keys_str_mv | AT mayarafernandamaggioli increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination AT mayarafernandamaggioli increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination AT mitchellpalmer increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination AT tylercthacker increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination AT hansmartinvordermeier increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination AT jodilmcgill increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination AT adamowhelan increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination AT michellehlarsen increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination AT williamrjacobs increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination AT wraywaters increasedtnfalphaifngammail2anddecreasedtnfalphaifngammaproductionbycentralmemorytcellsareassociatedwithprotectiveresponsesagainstbovinetuberculosisfollowingbcgvaccination |