CD40-CD40 Ligand Interactions in the Production of IL-12 and IFN-γ by Tuberculous Pleural Mononuclear Cells

  • Song, Chang-Hwa (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Nam, Hyun-Hee (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • An, Jeun-Ok (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Lee, Ji-Sook (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Kim, Hwa-Jung (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Park, Jeong-Kyu (Department of Microbiology, College of Medicine, Chungnam National University) ;
  • Suhr, Ji-Won (Department of Internal Medicine, Catholic University) ;
  • Jung, Sung-Soo (Department of Internal Medicine, College of Medicine, Chungnam National University) ;
  • Na, Moon-Jun (Department of Internal Medicine, College of Medicine, Konyang University) ;
  • Paik, Tae-Hyun (Department of Microbiology, College of Medicine, Konyang University) ;
  • Jo, Eun-Kyeong (Department of Microbiology, College of Medicine, Chungnam National University)
  • Published : 2002.09.30

Abstract

Background: Our previous study showed that purified protein derivative (PPD)-stimulated pleural mononuclear cells (PMC) from tuberculous pleurisy (Tbp) produced significantly more $IFN-{\gamma}$ (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 $IFN-{\gamma}$ production by altering IL-12 levels. Methods: IL-12 and $IFN-{\gamma}$ 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 PPO antigen (Ag). Results: Neutralization of CD80, CD86 and CD80+86 did not decrease $IFN-{\gamma}$ and IL-12 production in Tbp-PMC, whereas neutralization of CD40L significantly depressed IL-12 p40 and $IFN-{\gamma}$. In addition, neutralization of CD40L completely inhibited IL-12 p40 and $IFN-{\gamma}$ mRNA expression. Conclusion: The CD40-CD40L interaction might play a major role in IL-12 and $IFN-{\gamma}$ production in Tbp-PMC, thus contributing to protective immunity in human tuberculosis.

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Acknowledgement

Supported by : Ministry of Health & Welfare