Intrathymic alloantigen-mediated, tolerant, completely major histocompatibility complex-mismatched mouse hearts are specifically rejected by adoptively transferred anti-class I Ld+-specific 2C cells

Background. Tolerance to cardiac allografts can be induced in mice and rats by the injection of donor alloantigen into the thymus in combination with a CD4 T-cell-depleting antibody. GD8(+) cells in these animals are hyporesp onsive to graft-specific alloantigens. Most of the CD8(+) T cells in the tr ansgenic 2C mouse express a T-cell receptor specific for the class I major histocompatibility complex Ld+ locus. This study was designed to determine whether the adoptive transfer of these 2C T cells could precipitate rejecti on of a tolerant, completely major histocompatibility complex-mismatched Ld + or Ld- heart. Methods. C57BL/6 mice (Ld-) were given 10 x 10(6) cells of BALB/c (Ld+) or dm2 (BALB/c background lacking L-d [Ld-]) splenocytes intrathymically and G K1.5 (10 mg/kg) intraperitoneally. Twenty-one days later; BALB/c or dm2 hea rts were transplanted On the day of transplantation or after long term allo graft acceptance, recipients received naive 2C cells or 2C cells sensitized by in vitro mixed lymphocyte culture with BALB/c (Ld+). Results. Mean survival time of BALB/c cardiac allografts in untreated C57BL /6 mice was 7.3 days, although 73% of the mice that were pretreated with BA LB/c splenocytes IT plus GK1.5 accepted the donor antigen-specific heart al lografts indefinitely. All recipients that were pretreated with the intrath ymic plus GK1.5 and that were injected with naive 2C cells at the time of h eart transplantation experienced rejection of the BALB/c (Ld+), but not the dm2 (Ld-) hearts. In contrast, naive 2C cells could not reject tolerant (> 30 days acceptance) BALB/c (Ld+) hearts. 2C cells sensitized in vitro again st L-d were able to reject established BALB/c hearts but could not reject t he Ld- dm2 hearts. Conclusions. L-d-specific 2C T-cell receptor transgenic T cells that are ad optively transferred to recipients will precipitate the rejection of accept ed hearts that express class I Ld+ in mice rendered tolerant by an intrathy mic injection of alloantigen plus anti-CD4 monoclonal antibodies.