Immunogenicity of L(d+) transgenic mouse hearts

Area of Science:

• Immunology
• Transplantation Biology
• Cardiovascular Research

Background:

• Mice were engineered to express the L(d) gene in cardiac tissue using the alpha-myosin heavy chain promoter.
• These L(d+) transgenic mice served as a model to study immune responses against cardiac-specific antigens.

Purpose of the Study:

• To investigate immune reactivity against the cardiac L(d) transgene in a 'self' context.
• To assess the immunogenicity of the L(d+) transgene in transplanted hearts.
• To evaluate the response of non-transgenic C57BL/6 mice to L(d+) heart transplants.

Main Methods:

• Examined naïve L(d+) transgenic mice for signs of "autoimmunity."
• Adoptively transferred fresh or in vitro-sensitized L(d)-specific 2C cells into L(d+) transgenic mice.
• Analyzed heart-infiltrating lymphocytes using fluorescence-activated cell sorter (FACS).
• Transplanted L(d+) transgenic hearts into syngeneic C57BL/6 recipients.

Main Results:

• Naïve L(d+) transgenic mice showed no signs of lymphocytic infiltration or "autoimmunity."
• Adoptive transfer of 2C cells did not lead to rejection of the native L(d+) heart.
• In vitro-sensitized 2C cells showed significantly greater homing to L(d+) hearts compared to L(d-) hearts.
• Non-transgenic C57BL/6 mice rejected L(d+) heart transplants with a mean survival time of 17 days.
• Syngeneic C57BL/6 heart transplants were accepted indefinitely, confirming specific rejection of the L(d+) transgene.

Conclusions:

• The class I L(d) transgene, while not recognized by the host immune system in its native cardiac tissue, is immunogenic.
• Evidence of immunogenicity was demonstrated by the homing of anti-L(d) 2C cells to the heart.
• Transplantation of L(d+) hearts into syngeneic recipients resulted in rejection, further confirming the transgene's immunogenicity.