Indirect recognition of allopeptides promotes the development of cardiac allograft vasculopathy.

Graft loss from chronic rejection has become the major obstacle to the long-term success of whole organ transplantation. In cardiac allografts, chronic rejection is manifested as a diffuse and accelerated form of arteriosclerosis, termed cardiac allograft vasculopathy. It has been suggested that T-cell recognition of processed alloantigens (allopeptides) presented by recipient antigen-presenting cells through the indirect pathway of allorecognition plays a critical role in the development and progression of chronic rejection. However, definitive preclinical evidence to support this hypothesis is lacking. To examine the role of indirect allorecognition in a clinically relevant large animal model of cardiac allograft vasculopathy, we immunized MHC inbred miniature swine with synthetic polymorphic peptides spanning the alpha(1) domain of an allogeneic donor-derived swine leukocyte antigen class I gene. Pigs immunized with swine leukocyte antigen class I allopeptides showed in vitro proliferative responses and in vivo delayed-type hypersensitivity responses to the allogeneic peptides. Donor MHC class I disparate hearts transplanted into peptide-immunized cyclosporine-treated pigs not only rejected faster than unimmunized cyclosporine-treated controls (mean survival time = 5.5 +/-1.7 vs. 54.7 +/-3.8 days, P < 0.001), but they also developed obstructive fibroproliferative coronary artery lesions much earlier than unimmunized controls (<9 vs. >30 days). These results definitively link indirect allorecognition and cardiac allograft vasculopathy.

Alimentary tract involvement in Kaposi sarcoma: radiographic and endoscopic findings in 25 homosexual men.

An outbreak of Kaposi sarcoma has recently occurred among young homosexual men. It differs from the classic form in its virulence and preponderance of systemic manifestations. Twenty-five homosexual men with a mean age of 37 and biopsy-proven Kaposi sarcoma received extensive gastrointestinal evaluations. Twelve patients (48%) had evidence of gastrointestinal involvement by radiography and/or endoscopy. Lesions were found in the larynx, oropharynx, esophagus, stomach, duodenum, and colon. Radiographically they ranged from minimally elevated submucosal lesions, some with central ulceration, to polypoid defects. Abdominal CT was obtained in 18 patients, 11 of whom showed abnormalities. Of those with abnormal CT, 50% had retroperitoneal adenopathy. The gastrointestinal radiographic findings with endoscopic correlation in this unusual group of patients is discussed.