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Mechanisms underlying trypanosome-elicited immunosuppression.
Annales De La Societe Belge De Medecine Tropicale
|January 1, 1992
Summary
Trypanosoma brucei infection suppresses T-cell responses through two distinct macrophage-mediated mechanisms. These involve prostaglandin-induced suppression of IL-2 production and a separate pathway inhibiting IL-2 receptor expression, leading to immunosuppression.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Experimental infections with Trypanosoma brucei profoundly suppress T-cell proliferative responses in mice.
- This suppression is mediated by macrophages and involves complex regulatory mechanisms.
Purpose of the Study:
- To elucidate the distinct suppressive mechanisms contributing to T-cell dysfunction during Trypanosoma brucei infection.
- To investigate the roles of cytokines like prostaglandin, IL-2, IL-2R, IFN-gamma, and TNF-alpha in this process.
Main Methods:
- Analysis of lymph node cells from infected mice.
- Co-culture experiments with T. brucei-pulsed macrophages and T-cells.
- Assessment of cytokine production (IL-2, IFN-gamma, TNF-alpha) and cell surface receptor expression (IL-2R).
Main Results:
- Two unlinked suppressive mechanisms were identified: prostaglandin-mediated suppression of IL-2 production and a prostaglandin-independent suppression of IL-2 receptor expression.
- Interferon-gamma (IFN-gamma) produced by lymph node cells contributes to IL-2 receptor downregulation.
- T. brucei-pulsed macrophages induce CD8+ T-cell secretion of IFN-gamma, potentially via TNF-alpha.
Conclusions:
- Macrophage uptake of T. brucei generates suppressive cells that inhibit T-cell proliferation.
- The interaction releases TNF-alpha and IFN-gamma, which contribute to T-cell immunosuppression and may play a role in immunopathology.
- Understanding these mechanisms is crucial for addressing trypanosome-induced immune dysregulation.