title: Th2 lymphocyte clone can activate macrophage antileishmanial defense by a lymphokine-independent mechanism in vitro and can augment parasite attrition in vivo.
abstract: Antileishmanial defense has been ascribed to the antimicrobial effects induced by soluble macrophage-activating lymphokines (MAFs), such as interferon-gamma and granulocyte-macrophage colony-stimulating factor. Recently, we identified an additional mechanism of T cell-mediated macrophage activation of defense against Leishmania that is apparently lymphokine independent, requires cell-cell contact, and is not cytotoxic to host cells. By employing antigen-specific murine T cell hybridoma lines, we observed that this property was associated with CD4+ subpopulations possessing the characteristics of the Th1 subset. In the present study, we address the question of whether contact-mediated macrophage activation can also be induced by Th2 lymphocytes. We employed as T effector cells in antileishmanial defense assays the Th2 cell line D10.G1.4 (D10) which is specific for conalbumin. We observed that D10 cells were able to induce activation of Leishmania-infected macrophages only when the macrophages were also primed with conalbumin, and that this activation apparently occurred by a mechanism without the secretion of MAF. Moreover, when mice infected with L. major were injected into footpad lesions with conalbumin and D10 cells, in situ parasite replication was partially inhibited. The expression of this antimicrobial mechanism by Th1 as well as Th2 clones suggests that the property of contact-mediated (lymphokine-independent) activation may be shared by certain lymphocytes in both Th1 and Th2 subpopulations. We hypothesize that this activation mechanism may involve the interaction of a lymphocyte membrane-associated MAF (such as tumor necrosis factor) and its receptor on the infected macrophage, resulting in the induction of antimicrobial effects but not cytotoxicity to the host cell.
authors.affiliation: Department of Medicine, New England Medical Center Hospitals, Boston, Massachusetts.
authors.forename: J P
authors.initials: JP
authors.lastname: Sypek
authors.forename: M M
authors.initials: MM
authors.lastname: Matzilevich
authors.forename: D J
authors.initials: DJ
authors.lastname: Wyler
mesh_terms: D000818:Animals; D002450:Cell Communication; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007895:Leishmania tropica / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology* / Q000469:parasitology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor