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Monocytes are required to trigger Ca2+ uptake in the proliferative response of human t lymphocytes to staphylococcus
Abstract:
We have used the T-cell mitogen Staphylococcus aureus protein A (SpA) to study the role of monocytes in the early events of T-lymphocyte activation. The mitogenic response of human peripheral blood mononuclear cells (PBM) was compared to the response of populations enriched for T cells by E-rosetting (PBM-E+). In response to SpA, the [3H]thymidine uptake of PBM-E+ was reduced by 80% compared to PBM. The reduced response of PBM-E+ was completely restored by the addition of irradiated PBM-E- or the monocyte-like human cell line U-937 but not by addition of irradiated PBM-E+. A direct interaction of SpA with monocytes is important since proliferative responses could be generated by preincubation of U-937 with SpA followed by washing and subsequent addition to PBM-E+; incubation of PBM-E+ with SpA followed by washing and subsequent addition of U-937 did not result in a proliferative response. To further delineate the role of the monocyte, we examined the ability of soluble SpA, U-937, or U-937 preincubated with SpA to trigger Ca2+ flux into T lymphocytes, an early step in initiation of the proliferative response. SpA-pretreated U-937, but neither SpA nor monocytes alone, triggered Ca2+ movement into the T lymphocytes. This defines a new role for the monocyte in the early events of T-lymphocyte activation.
Insights
Monocytes play a crucial role in T-lymphocyte activation. Staphylococcus aureus protein A (SpA) requires monocyte interaction to effectively stimulate T-cell proliferation and calcium flux, highlighting monocytes
Area of Science:
- Immunology
- Cell Biology
Background:
- Monocytes are key immune cells involved in T-lymphocyte activation.
- Staphylococcus aureus protein A (SpA) is a known T-cell mitogen.
Purpose of the Study:
- To investigate the specific role of monocytes in early T-lymphocyte activation events induced by SpA.
- To elucidate the mechanism by which monocytes facilitate SpA-mediated T-cell responses.
Main Methods:
- Comparing mitogenic responses of human peripheral blood mononuclear cells (PBM) and T-cell enriched populations (PBM-E+).
- Assessing the effect of adding monocytes or monocyte-like cell lines (U-937) to T-cell populations.
- Investigating calcium (Ca2+) flux in T lymphocytes following interaction with SpA and monocytes.
Main Results:
- T-cell enriched populations showed significantly reduced proliferation in response to SpA.
- Monocyte addition restored SpA-induced T-cell proliferation.
- SpA-pretreated monocytes, but not SpA alone, triggered calcium flux in T lymphocytes.
Conclusions:
- Monocytes are essential for SpA-mediated T-lymphocyte proliferation.
- Direct interaction between SpA and monocytes is critical for initiating T-cell activation.
- Monocytes play a previously unrecognized role in triggering early calcium signaling events in T lymphocytes.