Macrophage activation for antileishmanial defense by an apparently novel mechanism.
Activation of macrophages by lymphokines (including interferon-gamma; IFN-gamma) is presently considered to be a major host defense mechanism against a number of intracellular microorganisms. In a series of earlier studies that made use of mice undergoing spontaneous resolution of footpad infections with Leishmania major, we obtained evidence suggesting that a subpopulation of Leishmania-sensitized lymph node T lymphocytes could activate antimicrobial effects in Leishmania-infected macrophages by an apparently lymphokine-independent mechanism. These effector lymphocytes are not cytotoxic to host cells, and their effects are antigen specific and genetically restricted. To more rigorously investigate this apparently novel mechanism of macrophage activation, we examined the effect of blocking lymphokine production with cyclosporin A (CSA) on the capacity of these effector lymphocytes to exert macrophage activating function. Although CSA blocked lymphokines that activate antileishmanial effects, it did not inhibit the antimicrobial capacity of the effector lymphocytes. We also confirmed that IFN-gamma is the major macrophage-activating lymphokine that induces antileishmanial effects; treatment of lymphokine-containing supernatants with anti-IFN-gamma antibody markedly reduced their antimicrobial effects. In contrast, treatment of effector lymphocytes with this antibody failed to reduce their macrophage-activating capacity. We conclude that there exists an apparently novel macrophage-activating mechanism for antimicrobial defense that is independent of soluble lymphokine mediators.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology; D003864:Depression, Chemical; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology*; D007895:Leishmania tropica / Q000254:growth & development / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology / Q000469:parasitology; D008222:Lymphokines / Q000096:biosynthesis; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D008222:Lymphokines; D007371:Interferon-gamma