TY - JOUR
T1 - Evaluating the role of tumor necrosis factor-alpha in experimental pulmonary tuberculosis in the guinea pig
AU - Lasco, Todd M.
AU - Cassone, Lynne
AU - Kamohara, Hidenobu
AU - Yoshimura, Teizo
AU - McMurray, David N.
N1 - Funding Information:
We thank Dr. Larry Dangott in the Protein Chemistry Laboratory at Texas A&M University for his technical assistance and sequencing of rgpTNF- α . This work was supported by National Institutes of Health Grant RO1 AI-15495 to D.N.M.
PY - 2005/7
Y1 - 2005/7
N2 - Tumor necrosis factor-α (TNF-α) is suggested to play multiple roles in immune and pathologic responses in tuberculosis. In this study, we have developed a system for the expression of recombinant guinea pig TNF-α (rgpTNF-α). Using rgpTNF-α along with neutralizing anti-rgpTNF-α antiserum, we tested the effect of modulating the levels of TNF-α on antigen-specific T cell proliferation in splenocytes. By neutralizing TNF-α in the supernatant of PPD-pulsed splenocytes with anti-rgpTNF-α, we observed hyperproliferation. Conversely, the addition of rgpTNF-α resulted in a significant suppression of PPD-induced lymphoproliferation. In addition, when unvaccinated and BCG-vaccinated guinea pigs were treated with polyclonal rgpTNF-α antiserum throughout the first 3 weeks following low-dose, pulmonary infection with Mycobacterium tuberculosis H37Rv, we observed splenomegaly in BCG-vaccinated guinea pigs. We also detected higher levels of splenic granuloma organization in the non-vaccinated group as well as a significant number of plasma cells associated with granulomata from the BCG-vaccinated group. These results suggest that modulating the availability of TNF-α in BCG-vaccinated guinea pigs can lead to immuno-dysregulation and, perhaps, the inappropriate enhancement of humoral immunity. Conversely, abrogating TNF-α activity in the context of a hyperinflammatory response in non-vaccinated guinea pigs may, in fact, rescue them from immunopathological consequences of overproducing TNF-α.
AB - Tumor necrosis factor-α (TNF-α) is suggested to play multiple roles in immune and pathologic responses in tuberculosis. In this study, we have developed a system for the expression of recombinant guinea pig TNF-α (rgpTNF-α). Using rgpTNF-α along with neutralizing anti-rgpTNF-α antiserum, we tested the effect of modulating the levels of TNF-α on antigen-specific T cell proliferation in splenocytes. By neutralizing TNF-α in the supernatant of PPD-pulsed splenocytes with anti-rgpTNF-α, we observed hyperproliferation. Conversely, the addition of rgpTNF-α resulted in a significant suppression of PPD-induced lymphoproliferation. In addition, when unvaccinated and BCG-vaccinated guinea pigs were treated with polyclonal rgpTNF-α antiserum throughout the first 3 weeks following low-dose, pulmonary infection with Mycobacterium tuberculosis H37Rv, we observed splenomegaly in BCG-vaccinated guinea pigs. We also detected higher levels of splenic granuloma organization in the non-vaccinated group as well as a significant number of plasma cells associated with granulomata from the BCG-vaccinated group. These results suggest that modulating the availability of TNF-α in BCG-vaccinated guinea pigs can lead to immuno-dysregulation and, perhaps, the inappropriate enhancement of humoral immunity. Conversely, abrogating TNF-α activity in the context of a hyperinflammatory response in non-vaccinated guinea pigs may, in fact, rescue them from immunopathological consequences of overproducing TNF-α.
KW - Granuloma
KW - Guinea pig
KW - Mycobacterium tuberculosis
KW - TNF-α
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U2 - 10.1016/j.tube.2005.01.001
DO - 10.1016/j.tube.2005.01.001
M3 - Article
C2 - 15958260
AN - SCOPUS:20444402654
VL - 85
SP - 245
EP - 258
JO - Bulletin of the International Union Against Tuberculosis and Lung Disease
JF - Bulletin of the International Union Against Tuberculosis and Lung Disease
SN - 1472-9792
IS - 4
ER -