Larvicidal properties of macrophages induced by cloned murine schistosomal egg antigen-specific CD4 positive T-helper lymphocytes

The role of T-helper (TH) lymphocytes in activating peritoneal macrophages (PM) to kill larvae of the helminth Schistosoma mansoni (schistosomula) was investigated with the use of egg antigen-specific CD4 positive TH clones of both the TH1 and TH2 types. Results showed that stimulated TH1 clones, in exceedingly small numbers, or supernatants thereof, conferred on PM the ability to kill schistosomula. The molecule responsible for PM activation was found to be interferon-gamma (IFN-gamma). IFN-gamma-induced PM larvicidal activity was dependent on live cells, energy, as well as protein synthesis, and appeared to be mediated by toxic nitrogen metabolites. In contrast, egg antigen-specific TH2 clones, or their supernants, failed to induce PM larval killing, as they did not secrete IFN-gamma, or any equivalent macrophage activating factor. We postulate a mechanism by which egg antigen-specific TH1 clones may be capable of playing a critical role in the resistance to schistosomal reinfection through IFN-gamma-mediated activation of macrophage helminthotoxicity.