Organ transplant specificity of tolerance to skin grafts with heart or kidney grafts plus nondepleting anti-CD4 monoclonal antibody (RIB 5/2) and intravenous donor alloantigen administration

Background. CD4+ T cells play an essential role in allograft rejection. Mon oclonal anti-rat CD4 antibody, RIB 5/2, has been shown to modulate the CD4 glycoprotein without eliminating recipient T cells. A single dose of monocl onal anti-rat CD4 antibody RIB 5/2 plus donor splenocytes results in donor- specific unresponsiveness to heart and kidney allografts, but not skin allo grafts. This study examined whether tolerance to the more resistant skin gr aft could also be achieved with RIB 5/2. Methods. Buffalo (RT1(b)) recipients were given a single dose (20 mg/kg) of monoclonal antibody RIB 5/2 IP plus TV Lewis (RT1(1)) splenocytes (25 x 10 (6)) 21 days before Lewis heart, kidney, or skin grafts. In addition, Lewis skin was grafted either simultaneously with or after long term Lewis heart or kidney allograft acceptance (> 50 days). Results. While IV alloantigen plus RIB 5/2 results in long-term acceptance of both heart and kidney, skin allografts are rejected when transplanted al one. Simultaneous transplantation with a Lewis kidney, but not with a Lewis heart, resulted in long-term Lewis skin graft acceptance. However, recipie nts tolerant to Lewis kidney or heart alone will not accept subsequent Lewi s skin grafts, while recipients of simultaneous Lewis skin and kidney graft s subsequently accept a second Lewis, but not third-party Brown Norway (RT1 (n)), skin graft. Conclusion. RIB 5/2 plus Lewis donor splenocytes tolerize for donor-specifi c heart and kidney but not skin grafts. However, Lewis skin grafted simulta neously with a Lewis kidney, but not Lewis heart, is accepted and protects a subsequent donor-specific Lewis skin graft. (C) 2001 Academic Press.