Cytokines and local cellular immunity.

Abstract

The characteristics and function of human lymphocytes at a morbid site were studied. Exudative-sensitized lymphocytes in tuberculous pleural fluid reacted to the specific antigen more effectively and produced higher titers of lymphokines including interferon gamma (IFN-gamma) and interleukin 2 (IL-2) 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 involve the production of lymphokines at the morbid site and they effectively exert local cellular immunity through the action of such lymphokines. Immunofluorescence study showed an increased production of inducible nitric oxide synthase (iNOS) and peroxynitrite in bacille de Calmette-Guérin (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 nitric oxide (NO) and its reactive product with the oxygen radical, peroxynitrite, could play an important role in BCG killing in human AM.