Endothelial cells expressing an inflammatory phenotype are lysed by superantigen-targeted cytotoxic T cells

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Endothelial cells (EC) play a role in tumor microvasculature.
• Superantigens, like staphylococcal enterotoxin A (SEA), can activate T cells.
• Targeting T cells to specific cell surface molecules is a goal in cancer immunotherapy.

Purpose of the Study:

• To investigate if staphylococcal enterotoxin A (SEA) can direct cytotoxic T cells to lyse cytokine-stimulated endothelial cells (EC).
• To determine if SEA-primed cytotoxic T cells can be targeted to EC surface molecules for cancer immunotherapy.

Main Methods:

• Human umbilical vein EC (HUVEC), dermal microvascular EC (HMVEC), and EA.hy926 cells were stimulated with gamma interferon (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha).
• SEA-primed T cells were used to induce cytotoxicity against activated EC.
• Fusion proteins of SEA variants and antibody fragments were used to target EC surface molecules.

Main Results:

• Cytokine-stimulated EC upregulated HLA class II, CD54, and CD106 expression.
• SEA-primed T cells induced significant cytotoxicity against activated EA.hy926 cells pre-incubated with SEA.
• Blocking CD54 abrogated T-cell-mediated attack.
• Fusion proteins enabled targeted lysis of EC by T cells, even when EC expressed unknown antigens.

Conclusions:

• Superantigen-activated T cells can induce endothelial cell (EC) killing when ECs exhibit an inflammatory phenotype.
• Targeting superantigens to specific EC surface molecules effectively induces T-cell-mediated EC lysis.
• This approach holds promise for directed T-cell-mediated lysis of proliferating EC in tumor microvasculature for clinical applications.