Immunogenicity of Ld+ transgenic mouse hearts

Background. C57BL/6 mice transfected with the L-d gene coupled to the alpha -myosin heavy chain promoter result in transgenic mice with L-d antigen ex pressed only on cardiac tissue. These transgenic animals allow the examinat ion of immune reactivity against cardiac L-d by "self" or by adoptively tra nsferred Ld specific 2C cells, and the response of nontransgenic C57BL/6 mi ce to the transplanted Ld+ heart. Methods. Naive cardiac Ld+ transgenic mice were examined for evidence of L- d "autoimmunity." Forty million fresh 2C cells or 2C cells sensitized in vi tro for 7 days against Balb/c (Ld+) + interleukin-2 were also given intrave nously to Ld+ transgenic mice. At 5 and 12 day's after injection, heart-inf iltrating lymphocytes were analyzed by fluorescence-activated cell sorter T he Ld+ transgenic hearts were also transplanted to syngeneic Ld- nontransge nic C57BL/6 to evaluate the heart immunogenicity. Results. Naive Ld+ transgenic mice did not exhibit any evidence of lymphocy tic infiltration on histologic examination. Adoptive transfer of either fre sh or in vitro sensitized 2C cells was also unable to reject the native Ld heart in transgenic mice (100% of the mice survived long term [more than 6 0 days]). Sensitization of the Ld+ transgenic mice with a Balb/c skin graft and interleukin-2 pump infusion (7 days) beginning 1 day before 2C cell in jection also did not promote rejection of the native Ld+ heart. However flu orescence-activated cell sorter analysis did reveal that a significantly gr eater number of in vitro sensitized 2C cells homed to the Ld+ but not Ld-, heart after both 5 and 12 days (P<.01, P<.001). In contrast, C57BL/6 mice r ejected the Ld+ (C57BL/6 background) transgenic heart in a mean survival of 17 +/-9.7 days (P<.01), whereas a syngeneic C57BL/6 heart transplant was a ccepted indefinitely. Lymphocytic infiltration consistent with rejection wa s present in all animals receiving Ld+ transgenic heart transplant, whereas no infiltrate was present in those receiving a syngeneic C57BL/6 heart tra nsplant. Conclusions. Although the class I L-d transgene is not recognized in its na tive host, its immunogenicity is shown by the homing of anti-L-d 2C cells t o the heart in situ and rejection of Ld+ heart grafts when transplanted int o syngeneic C57BL/6 mice.