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Song, Nam, An, Lee, Kim, Park, Suhr, Jung, Na, Paik, and Jo: CD40-CD40 Ligand Interactions in the Production of IL-12 and IFN-γ by Tuberculous Pleural Mononuclear Cells

Abstract

Background

Our previous study showed that purified protein derivative (PPD)-stimulated pleural mononuclear cells (PMC) from tuberculous pleurisy (Tbp) produced significantly more IFN-γ (10- to 70-fold) after in vitro PPD stimulation than freshly isolated pleural cells from malignant pleurisy. The present study was designed to determine whether blocking the CD40-CD40 ligand (CD40L) interaction decreases IFN-γ production by altering IL-12 levels.

Methods

IL-12 and IFN-γ production after neutralizing anti-CD40L antibody treatment was compared to the efficacy of anti-CD80, anti-CD86, and a combination of anti-CD80 and CD86 (CD80+86) monoclonal antibodies (mAb). These activities were measured by enzyme-linked immunosorbent assays (ELISAs) and reverse transcription-polymerase chain reaction (RT-PCR), after in vitro stimulation with PPD antigen (Ag).

Results

Neutralization of CD80, CD86 and CD80+86 did not decrease IFN-γ and IL-12 production in Tbp-PMC, whereas neutralization of CD40L significantly depressed IL-12 p40 and IFN-γ. In addition, neutralization of CD40L completely inhibited IL-12 p40 and IFN-γ mRNA expression.

Conclusion

The CD40-CD40L interaction might play a major role in IL-12 and IFN-γ production in Tbp-PMC, thus contributing to protective immunity in human tuberculosis.

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