Recombinant guinea pig TNF-α enhances antigen-specific type 1 T lymphocyte activation in guinea pig splenocytes

SummaryTNF-α is a principal pro-inflammatory cytokine which contributes to the activation of innate immunity and the transition to antigen-specific adaptive immunity in tuberculosis. Using recombinant guinea pig (rgp) TNF-α, the effect of TNF-α on lymphocyte activation was examined in unvaccinated and BCG-vaccinated guinea pigs. Splenocytes were stimulated with PPD or ConA, in the presence or absence of rgp TNF-α for 96 h. Lymphocyte proliferation was measured using [3H]thymidine uptake, and IL-12 p40 and IFN-γ mRNA were analyzed using real-time PCR. rgpTNF-α alone was able to stimulate a significant degree of proliferation in splenocytes. The addition of rgpTNF-α to PPD-stimulated cells enhanced the proliferation of splenocytes from BCG-vaccinated guinea pigs. Furthermore, enhancement of proliferation by rgpTNF-α was found to be correlated with upregulation of the levels of Type 1 cytokine mRNA (IL-12p40 and IFN-γ) in splenocyte cultures. This suggests that TNF-α plays an important role in the regulation of Type 1 T cell-mediated immune responses in the guinea pig.