Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 245-258 |
| Number of pages | 14 |
| Journal | Tuberculosis |
| Volume | 85 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jul 2005 |
| Externally published | Yes |
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Keywords
- Granuloma
- Guinea pig
- Mycobacterium tuberculosis
- TNF-α
ASJC Scopus subject areas
- Applied Microbiology and Biotechnology
- Microbiology
- Immunology and Allergy
- Infectious Diseases
- veterinary(all)
Cite this
Evaluating the role of tumor necrosis factor-alpha in experimental pulmonary tuberculosis in the guinea pig. / Lasco, Todd M.; Cassone, Lynne; Kamohara, Hidenobu; Yoshimura, Teizo; McMurray, David N.
In: Tuberculosis, Vol. 85, No. 4, 07.2005, p. 245-258.Research output: Contribution to journal › Article
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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.
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
UR - http://www.scopus.com/inward/record.url?scp=20444402654&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20444402654&partnerID=8YFLogxK
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 - Tuberculosis
JF - Tuberculosis
SN - 1472-9792
IS - 4
ER -