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Soluble TNF and membrane TNF expressed on CD4 + T lymphocytes differ In their ability to activate macrophage antileishmanial defense
Author(s) -
Birkland Timothy P.,
Sypek Joseph P.,
Wyler David J.
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.51.3.296
Subject(s) - biology , lymphokine , macrophage , tumor necrosis factor alpha , cytotoxic t cell , secretion , macrophage activating factor , effector , leishmania , cytokine , interferon gamma , microbiology and biotechnology , immune system , leishmania major , intracellular parasite , immunology , in vitro , biochemistry , parasite hosting , world wide web , computer science
In our studies of host defense against the intracellular parasite Leishmania major , we obtained evidence for a novel mechanism of macrophage activation for antimicrobial defense that involves direct cell contact between CD4 + T lymphocytes and Leishmania‐infected macrophages. The mechanism is distinctive as it does not involve secretion of lymphokines but is apparently mediated by the membrane‐anchored form of tumor necrosis factor (mTNF; ~50–60 kd) present on the surface of the effector T lymphocytes. Furthermore, it is not cytotoxic to the host cell and its expression is antigen specific and genetically restricted. We prepared a Leishmania ‐specific cloned T‐T cell hybridoma line 1B6 (CD4 + TH1) that expresses membrane‐bound TNF but does not secrete TNF or other macrophage activators. We now report that 1B6 cells can activate antileishmanial defense in inflammatory macrophages, whereas soluble recombinant murine TNF (sTNF) alone is unable to do so. On the other hand, both 1B6 cells and sTNF can act synergistically with recombinant murine interferon‐γ (IFN‐γ, a known soluble macrophage‐activating factor) in activating antimicrobial defense and NO − 2 release. The effects of 1B6 alone and the synergistic effects of 1B6 and IFN‐γ or sTNF and IFN‐γ are arginine dependent. These results suggest that mTNF may be more efficient than sTNF in macrophage activation and that contact with effector CD4 + lymphocytes that express mTNF may be an important mechanism of host defense.