Analysis of Immunologic Mechanisms of High Natural Killer Cell Activity in Tuberculous Pleural Effusions

Abstract

We found natural killer (NK) activity to be high in tuberculous pleural effusions from which Mycobacterium tuberculosis was cultured. In this study, we investigated and compared the mechanisms of this NK activity in tuberculous pleural effusions and peripheral blood. Cytotoxicity was augmented in tuberculous pleural effusion mononuclear cells (PEMNC) and peripheral blood mononuclear cells (PBMNC) by culture with purified protein derivative (PPD). Prior to culture with PPD, there were many more interleukin-2 receptors (IL-2R, p55) on Leu 11+ (CD16+) cells in tuberculous PEMNC than in tuberculous PBMNC. After 5 days of culture with PPD, the numbers of IL-2R increased in both PEMNC and PBMNC. PPD-induced cytotoxicity was inhibited by the addition of anti-IL-2R monoclonal antibody (anti-IL-2R mAb). Interferon-gamma (IFN-gamma) production was abundant in the supernatants of cultured tuberculous PEMNC and PBMNC, but very little interleukin-2 (IL-2) and IFN-alpha and -beta were produced. Considerably more IFN-gamma was produced in tuberculous PEMNC than in tuberculous PBMNC, and PPD-induced cytotoxicity was inhibited by anti-IFN-gamma monoclonal antibody (anti-IFN-gamma mAb). Cell surface analysis after PPD-induced cytotoxicity was performed by complement-mediated cytolysis. Leu 11+ cells exhibited essential cytotoxicity in the induction and effector phases, but neither OKT4+ (CD4+) nor OKT8+ (CD8+) cells displayed such cytotoxicity. These data suggest that Leu 11+ cells in tuberculous PEMNC are activated by M. tuberculosis through IFN-gamma and that IL-2R plays an important role in the activation of NK cells.