TY - JOUR
T1 - Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties
AU - Metcalfe, Hannah J.
AU - Biffar, Lucia
AU - Steinbach, Sabine
AU - Guzman, Efrain
AU - Connelley, Tim
AU - Morrison, Ivan
AU - Vordermeier, H. Martin
AU - Villarreal-Ramos, Bernardo
PY - 2018/5/11
Y1 - 2018/5/11
N2 - There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4+ T cells post-boosting. Here, the capacity of Ag85A-specific CD4+ T cell lines – derived before and after viral boosting – to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4+ T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4+ T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology.
AB - There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4+ T cells post-boosting. Here, the capacity of Ag85A-specific CD4+ T cell lines – derived before and after viral boosting – to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4+ T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4+ T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology.
KW - Antigen specific
KW - Cytokines
KW - Mycobacteria killing
KW - T-cell lines
UR - http://www.scopus.com/inward/record.url?scp=85045203193&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2018.03.068
DO - 10.1016/j.vaccine.2018.03.068
M3 - Article
C2 - 29655632
AN - SCOPUS:85045203193
SN - 0264-410X
VL - 36
SP - 2850
EP - 2854
JO - Vaccine
JF - Vaccine
IS - 20
ER -