Evaluating the role of tumor necrosis factor-alpha in experimental pulmonary tuberculosis in the guinea pig.
Tumor necrosis factor-alpha (TNF-alpha) 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-alpha (rgpTNF-alpha). Using rgpTNF-alpha along with neutralizing anti-rgpTNF-alpha antiserum, we tested the effect of modulating the levels of TNF-alpha on antigen-specific T cell proliferation in splenocytes. By neutralizing TNF-alpha in the supernatant of PPD-pulsed splenocytes with anti-rgpTNF-alpha, we observed hyperproliferation. Conversely, the addition of rgpTNF-alpha resulted in a significant suppression of PPD-induced lymphoproliferation. In addition, when unvaccinated and BCG-vaccinated guinea pigs were treated with polyclonal rgpTNF-alpha 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-alpha in BCG-vaccinated guinea pigs can lead to immuno-dysregulation and, perhaps, the inappropriate enhancement of humoral immunity. Conversely, abrogating TNF-alpha activity in the context of a hyperinflammatory response in non-vaccinated guinea pigs may, in fact, rescue them from immunopathological consequences of overproducing TNF-alpha.
Lasco
Todd M
TM
Department of Medical Microbiology and Immunology, The Texas A&M University System-Health Science Center, College Station, TX 77843-1114, USA. tlasco@mycoresearch.com
Cassone
Lynne
L
Kamohara
Hidenobu
H
Yoshimura
Teizo
T
McMurray
David N
DN
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001500:BCG Vaccine / Q000276:immunology; D001483:Base Sequence; D015153:Blotting, Western; D006099:Granuloma / Q000276:immunology / Q000382:microbiology; D006168:Guinea Pigs; D008213:Lymphocyte Activation; D009163:Mycobacterium bovis / Q000276:immunology*; D013163:Splenomegaly / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D001500:BCG Vaccine; D014409:Tumor Necrosis Factor-alpha