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Human endothelial cells induce and regulate cytolytic T cell differentiation
1Program in Molecular Cardiobiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 30, 1998
Summary
Human endothelial cells (EC) are less efficient at stimulating cytotoxic T lymphocytes (CTL) than B lymphoblastoid cells (BLC). EC also actively suppress the development of anti-BLC CTL, suggesting a regulatory role in T cell responses.
Area of Science:
- Immunology
- Cell Biology
- T cell differentiation
Background:
- Cytotoxic T lymphocytes (CTL) are crucial for adaptive immunity, mediating the killing of target cells.
- The differentiation of CTL is influenced by the type of antigen-presenting cell and its stimulatory capacity.
- Endothelial cells (EC) and B lymphoblastoid cells (BLC) differ in their expression of co-stimulatory molecules, potentially affecting T cell activation.
Purpose of the Study:
- To compare the capacity of human endothelial cells (EC) versus B lymphoblastoid cells (BLC) to stimulate allogeneic CD8+ T cells into CTL.
- To investigate the impact of input cell number on CTL specificity, potency, and phenotype.
- To determine the regulatory role of EC in T cell responses, particularly in the context of co-stimulation with BLC.
Main Methods:
- Co-culture of allogeneic CD8+ T cells with varying numbers of EC or BLC.
- Assays for allorestricted cytotoxicity, T cell proliferation, IFN-gamma secretion, and perforin expression.
- Evaluation of CTL responses when T cells were cultured with EC and BLC together, including assessment of EC-conditioned medium effects.
Main Results:
- EC are less efficient stimulators of CTL differentiation compared to BLC from the same donor, regardless of input cell number.
- Optimal CTL development against EC occurred at intermediate input cell numbers (1.0-2.5 x 10^5 cells/well), yielding MHC class I-restricted, CD8+, perforin-positive CTL.
- EC actively suppressed the differentiation of anti-BLC CTL when co-cultured with BLC, an effect mediated by soluble factors in EC-conditioned medium, while the anti-EC response remained intact.
Conclusions:
- Human EC are competent, but less efficient, activators of CTL differentiation than BLC.
- EC possess a regulatory function that actively suppresses the differentiation and/or expansion of allospecific CTL, particularly in the presence of other stimulatory cells like BLC.
- The findings highlight the nuanced role of different antigen-presenting cells in shaping adaptive immune responses.