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

Mayara F. Maggioli, Mitchell V. Palmer, Tyler C. Thacker, Hans Martin Vordermeier, Jodi L. McGill, Adam O. Whelan, Michelle H. Larsen, William R. Jacobs, W. Ray Waters

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 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 (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.

Original languageEnglish (US)
Article number421
JournalFrontiers in Immunology
Volume7
Issue numberOCT
DOIs
StatePublished - Oct 17 2016

Fingerprint

Bovine Tuberculosis
Interferons
Interleukin-2
Vaccination
Tumor Necrosis Factor-alpha
T-Lymphocytes
Mycobacterium bovis
Antigens
Cytokines
Mycobacterium Infections
T-Lymphocyte Subsets
Aerosols
Immunity
Flow Cytometry
Tuberculosis
Vaccines
Infection
Population

Keywords

  • Bovine tuberculosis
  • Calf model
  • Central memory T cells
  • Polyfunctional T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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. / Maggioli, Mayara F.; Palmer, Mitchell V.; Thacker, Tyler C.; Vordermeier, Hans Martin; McGill, Jodi L.; Whelan, Adam O.; Larsen, Michelle H.; Jacobs, William R.; Waters, W. Ray.

In: Frontiers in Immunology, Vol. 7, No. OCT, 421, 17.10.2016.

Research output: Contribution to journalArticle

Maggioli, Mayara F. ; Palmer, Mitchell V. ; Thacker, Tyler C. ; Vordermeier, Hans Martin ; McGill, Jodi L. ; Whelan, Adam O. ; Larsen, Michelle H. ; Jacobs, William R. ; Waters, W. Ray. / 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. In: Frontiers in Immunology. 2016 ; Vol. 7, No. OCT.
@article{2ad91c3842dd4a668ab5ef240f357695,
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 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 (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.",
keywords = "Bovine tuberculosis, Calf model, Central memory T cells, Polyfunctional T cells",
author = "Maggioli, {Mayara F.} and Palmer, {Mitchell V.} and Thacker, {Tyler C.} and Vordermeier, {Hans Martin} and McGill, {Jodi L.} and Whelan, {Adam O.} and Larsen, {Michelle H.} and Jacobs, {William R.} and Waters, {W. Ray}",
year = "2016",
month = "10",
day = "17",
doi = "10.3389/fimmu.2016.00421",
language = "English (US)",
volume = "7",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "OCT",

}

TY - JOUR

T1 - 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

AU - Maggioli, Mayara F.

AU - Palmer, Mitchell V.

AU - Thacker, Tyler C.

AU - Vordermeier, Hans Martin

AU - McGill, Jodi L.

AU - Whelan, Adam O.

AU - Larsen, Michelle H.

AU - Jacobs, William R.

AU - Waters, W. Ray

PY - 2016/10/17

Y1 - 2016/10/17

N2 - 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 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 (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.

AB - 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 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 (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.

KW - Bovine tuberculosis

KW - Calf model

KW - Central memory T cells

KW - Polyfunctional T cells

UR - http://www.scopus.com/inward/record.url?scp=84997525081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84997525081&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2016.00421

DO - 10.3389/fimmu.2016.00421

M3 - Article

VL - 7

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - OCT

M1 - 421

ER -