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Tumor necrosis factor alpha: a costimulator for cytotoxic cell differentiation
1Cytokines et immunité antitumorale URA 1156, CNRS, Institut Gustave Roussy, Villejuif, France.
Nouvelle Revue Francaise D'Hematologie
|January 1, 1991
Summary
Tumor Necrosis Factor alpha (TNF) synergizes with Interleukin-2 (IL-2) to activate immune cells. TNF enhances IL-2 signaling, boosting the generation and function of cytotoxic T cells and lymphokine-activated killer cells.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Biology
Background:
- Large granular lymphocytes (LGL) are activated by Interleukin-2 (IL-2) into lymphokine-activated killer (LAK) cells.
- Tumor Necrosis Factor alpha (TNF) plays a role in immune responses.
Purpose of the Study:
- To investigate the synergistic effects of IL-2 and TNF on LAK and cytotoxic T lymphocyte (CTL) generation.
- To elucidate the role of TNF in IL-2-mediated immune cell activation.
Main Methods:
- Activation of LGL with IL-2 and TNF.
- Assessment of LAK activity.
- Generation of alloreactive CTL in mixed lymphocyte reactions.
- Inhibition studies using anti-TNF antibodies.
Main Results:
- Low doses of IL-2 failed to induce LAK generation without TNF.
- TNF is a potential physiological mediator in LGL to LAK differentiation.
- Exogenous TNF enhanced IL-2-induced CTL generation.
- TNF potentiates IL-2 signaling, potentially enhancing serine esterase activity.
Conclusions:
- TNF acts synergistically with IL-2 to enhance immune cell activation.
- TNF may increase IL-2 signaling efficiency for cytotoxic T cell generation.
- TNF is a key mediator in the sequential activation of LGL into LAK effectors.