Pretreatment with portal venous ultraviolet B irradiated donor alloantigenpromotes donor-specific tolerance to rat nerve allografts

Objective: To determine if a single intraportal inoculation of ultraviolet B-irradiated (UVB) donor splenocytes can prevent nerve allograft rejection and confer donor-specific immunotolerance to rat nerve allograft segments. Methods: Age-matched, class I and class II major histocompatibility complex (MHC) mismatched Buffalo (RT1(b)) rats were transplanted with a syngeneic nerve isograft, a Lewis (RT1(1)) nerve allograft, or a Brown-Norway (RT1(n) ) rat nerve allograft segment. Control Buffalo rats in group I received a 3 .0-cm Lewis (RT11) sciatic-posterior tibial interposition nerve allograft w ithout pretreatment; group II Buffalo rats received a syngeneic Buffalo ner ve isograft without pretreatment. Group III Buffalo recipients were inocula ted with 2.5 x 10(7) UVB-irradiated Lewis donor splenocyte cells by portal venous administration 7 days before transplantation with a 3.0-cm sciatic-p osterior tibial nerve allograft from a Lewis (RT11) or a third party Brown- Norway rat (RT1(n)) donor (group IV). Nerve graft regeneration was assessed with walking track analysis, nerve conduction studies, retrograde neural t racing, nerve graft histology, and morphometry. Recipient immune tolerance was assessed through in vitro immunological assessment, Results: Pretreatme nt with UVB-irradiated donor splenocytes 7 days before transplantation prev ented ner-ve allograft rejection. Pretreated animals receiving a nerve allo graft recovered limb function, and demonstrated morphological, histological , and electrophysiologic parameters of nerve regeneration similar to that m easured in rats receiving a nerve isograft. In vitro immunological assessme nt by mixed lymphocyte culture (MLC), cytotoxic T lymphocyte (CTL) assay, l imiting dilution analysis (LDA) of helper (pTH) and cytotoxic (pCTL) precur sor frequencies, and IL-2 production demonstrated a marked donor-specific s uppression in allografted animals pretreated with intraportal UVB-irradiate d donor splenocytes. These assessments correlated with indefinite acceptanc e of donor nerve allografts. Conclusions: A single pretreatment with a sing le intraportal dose of UVB-modified donor antigen specifically induces tole rance to peripheral nerve allografts in rats.