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Feedback suppression of staphylococcal enterotoxin-stimulated T-lymphocyte proliferation by macrophages through
1Department of Immunology, Nagoya University School of Medicine, Japan.
Abstract:
Staphylococcal enterotoxin A (SEA)- or SEB-stimulated T-lymphocyte proliferation was suppressed by the addition of high numbers of murine peritoneal macrophages or rat peritoneal or alveolar macrophages, whereas lower numbers of murine peritoneal macrophages enhanced the T-lymphocyte response. Suppression was associated with the increase of accumulation of nitrite, a product of nitric oxide, in the culture supernatants. This macrophage-mediated suppression was totally reversed by the addition of NG-monomethyl-L-arginine, a homolog of L-arginine, indicating that macrophage-mediated suppression of T-lymphocyte proliferation was mediated through the nitric oxide-synthesizing pathway activity. Macrophages in large numbers spontaneously produced nitric oxide in culture supernatant fluids. By the addition of autologous or allogeneic spleen cells but not thymocytes to SEA- or SEB-stimulated macrophage culture, nitric oxide production was greatly increased. When T lymphocytes in spleen cells were killed by antibody before addition to macrophage culture, nitric oxide production was diminished to the basal level. These results suggest that in addition to the action to support the process of T-lymphocyte activation by SEA or SEB, macrophages display a feedback regulatory action on the SEA- or SEB-stimulated T-cell proliferative response by releasing nitric oxide through interaction between macrophages and activated T lymphocytes.
Insights
High numbers of macrophages suppress T-lymphocyte proliferation via nitric oxide production. This feedback mechanism regulates immune responses to Staphylococcal enterotoxins A and B.
Area of Science:
- Immunology
- Cell Biology
Background:
- Staphylococcal enterotoxins A (SEA) and B (SEB) stimulate T-lymphocyte proliferation.
- Macrophages play a complex role in immune responses, with potential roles in both activation and suppression.
Purpose of the Study:
- To investigate the role of macrophages in regulating T-lymphocyte proliferation stimulated by SEA and SEB.
- To elucidate the mechanism behind macrophage-mediated suppression of T-lymphocyte responses.
Main Methods:
- Co-culture of T-lymphocytes with varying numbers of macrophages.
- Measurement of T-lymphocyte proliferation.
- Quantification of nitrite accumulation in culture supernatants as an indicator of nitric oxide production.
- Assessment of the effect of NG-monomethyl-L-arginine on T-lymphocyte suppression.
- Investigation of nitric oxide production in response to spleen cells and thymocytes.
Main Results:
- High numbers of macrophages suppressed SEA- or SEB-stimulated T-lymphocyte proliferation, while lower numbers enhanced it.
- Suppression correlated with increased nitrite (nitric oxide) accumulation.
- Macrophage-mediated suppression was reversed by NG-monomethyl-L-arginine, implicating nitric oxide synthesis.
- Nitric oxide production was enhanced by spleen cells (containing T-lymphocytes) but not thymocytes.
- Depletion of T-lymphocytes from spleen cells reduced nitric oxide production.
Conclusions:
- Macrophages exhibit feedback regulation on SEA- or SEB-stimulated T-cell proliferation.
- This regulation involves the release of nitric oxide through interactions between macrophages and activated T-lymphocytes.
- Nitric oxide production by macrophages is influenced by the presence of activated T-lymphocytes.