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Fas (CD95)/Fas ligand interactions regulate antigen-specific, major histocompatibility complex-restricted T/B cell
M Ozdemirli1, M El-Khatib, L C Foote
1Arthritis Center, Department of Pathology, Boston University School of Medicine, MA 02118, USA.
Insights
Fas ligand (FasL) cytotoxicity negatively regulates T and B cell collaboration. Inhibiting FasL with Fas-Ig enhances immune cell proliferation, suggesting Fas-Ig as an immunopotentiating agent.
Area of Science:
- Immunology
- Cell Biology
Background:
- T/B cell collaboration is crucial for adaptive immunity.
- Fas ligand (FasL) mediated cytotoxicity plays a role in immune regulation.
Purpose of the Study:
- To investigate the impact of FasL cytotoxicity on T/B cell collaboration in vitro.
- To evaluate the role of different B cell activation pathways on FasL sensitivity.
- To assess the immunomodulatory potential of Fas-Ig as a FasL inhibitor.
Main Methods:
- In vitro co-culture of cloned T helper 1 cells and antigen-pulsed, activated B cells.
- Comparison of B cells activated via IgM, CD14, and CD40 receptors.
- Utilizing Fas-Ig fusion protein to block FasL-mediated cytotoxicity.
Main Results:
- T and B cell proliferation correlated with B cell resistance to FasL cytotoxicity.
- FasL inhibition using Fas-Ig significantly enhanced both T and B cell proliferation.
- Activated B cell populations exhibited varying sensitivity to FasL-mediated killing.
Conclusions:
- FasL cytotoxicity acts as a negative regulator of T and B cell proliferation.
- Fas-Ig demonstrates potential as an immunopotentiating agent for T and B cell immunity.
- Modulating FasL activity can influence adaptive immune responses.
Abstract:
The effect of Fas ligand (FasL) cytotoxicity on T/B collaboration was examined in vitro using cloned T helper 1 cells and antigen-pulsed, activated B cells. We compared antigen-pulsed B cells that had been activated through different membrane receptors (IgM, CD14 and CD40) for their ability to induce T cell proliferation and to respond to T cell help. We also used a Fas-Ig fusion protein, an inhibitor of FasL-mediated cytotoxicity, to determine the effect of FasL cytotoxicity on the T and B cell proliferative responses. The data show that the extent of both T and B cell proliferative responses correlate with the relative resistance of activated B cell populations to FasL cytotoxicity. Moreover, both T and B cell proliferation could be enhanced by Fas-Ig. Our results demonstrate that FasL cytotoxicity is a negative regulatory mechanism for both T and B cell proliferative responses and that Fas-Ig can be an immunopotentiating agent for both T and B cell immunity.