[Tuberculous infection and biological response in man]

Abstract

The characteristics and function of human lymphocytes in tuberculous morbid site were studied. Exudative-sensitized lymphocytes in tuberculous pleural fluid reacted to the specific antigen more effectively and produced higher titers of cytokines including interferon gamma (IFN-gamma) than circulating lymphocytes. CD4+/CD8- T-cell subset is responsible for the antigen-specific IFN-gamma production in pleural T lymphocytes of patients with tuberculous pleurisy. Thus, activated T lymphocytes concern the production of cytokines at the morbid site and they effectively exert local cellular immunity through the action of such cytokines. Immunofluorescence study showed increased production of inducible nitric oxide synthase (iNOS) and peroxynitrite in BCG-inoculated human alveolar macrophages (AM). Reverse transcriptase-polymerase chain reaction methods also revealed the higher expression of iNOS-coding mRNA. Colony assay demonstrated that human AM effectively killed BCG in their cytoplasm. However, treatment of AM with NG-monomethyl-L-arginine monoacetate resulted in markedly reduced killing activity. These results clearly show that BCG-induced NO and its reactive product with the oxygen radical, peroxynitrite, could play an important role in BCG killing in human AM. We measured the pleural concentrations of IFN-gamma, interferon-gamma-inducing cytokines; interleukin (IL)-12 and IL-18 and interferon-gamma-inducible chemokines; IFN-gamma-inducible protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T cell alpha chemoattractant (I-TAC). These cytokines and chemokines in tuberculous pleural effusions were much higher than those in malignant pleural effusions. These findings indicate that IFN-gamma plays an important role in the cell mediated immunity in tuberculosis.