Endothelial cells present antigens in vivo

Area of Science:

• Immunology
• Vascular Biology
• Transplantation Immunology

Background:

• Immune recognition of vascular endothelial cells (EC) is crucial for allograft rejection, pathogen defense, and lymphocyte recruitment.
• EC are widespread but not predominant in any single tissue, making direct immune recognition studies challenging.
• This study investigated in vivo antigen presentation by EC using transgenic mice expressing beta-galactosidase (beta-gal) in their EC.

Purpose of the Study:

• To determine if vascular endothelial cells (EC) can present antigens in vivo.
• To investigate the immune response to EC-expressed antigens in transgenic mouse models.
• To understand the role of EC antigen presentation in immune tolerance and activation.

Main Methods:

• Generated TIE2-lacZ and VWF-lacZ transgenic mice expressing beta-galactosidase (beta-gal) exclusively in EC.
• Immunized transgenic and wild-type mice with beta-gal DNA or protein.
• Assessed immune responses including antibody titers, T cell proliferation, cytokine secretion, and graft survival.
• Transplanted skin and hearts between transgenic and wild-type mice.

Main Results:

• Immunization of transgenic mice induced robust, comparable immune responses to beta-gal, with no adverse health effects or vascular abnormalities.
• T cells from immunized mice showed proliferation and cytokine production in response to beta-gal.
• Transplanted hearts from transgenic donors into wild-type recipients showed normal function and graft EC expressed beta-gal, suggesting tolerance.
• Skin grafts from TIE2-lacZ mice onto FVB mice led to loss of beta-gal+ EC and development of anti-beta-gal antisera, indicating immune activation.
• Skin grafts from TIE2-lacZ onto VWF-lacZ mice retained beta-gal+ EC without antisera development, suggesting host tolerance.

Conclusions:

• Resting EC expressing beta-gal induce tolerance to specific lymphocytes that would otherwise react to EC-expressed antigens in transplanted skin.
• EC effectively present intracellular self-proteins to the immune system.
• Antigen presentation by EC does not lead to deletion or anergy of lymphocytes primed by conventional immunization.
• Immune recognition of EC exhibits context sensitivity, crucial for understanding and treating vascular-related immune diseases.