Immune Unresponsiveness by Intraportal UV-B-Irradiated Donor Antigen Administration Requires Persistence of Donor Antigen in a Nerve Allograft Model

The purpose of this study was to characterize the mechanism of unresponsiveness produced by the intraportal administration of ultraviolet-B (UV-B)-irradiated donor antigen. Pretreated Buffalo rats accepted Lewis nerve allografts, had decreased in vitro T-cell reactivity, and demonstrated nerve regeneration and recovery of limb function, while rejecting third-party nerve allografts. Regenerated nerve grafts were then retransplanted into a second naïve recipient. Rejection of the retransplanted allograft by naïve donor-strain, but not recipient-strain, animals suggests that the allografts were completely replaced by host tissue. Pretreated Buffalo rats were also given a second Lewis allograft after the first had regenerated. The second allograft was rejected and in vitro immune reactivity was comparable to naïve animals. Because the unresponsiveness state was extinguished with loss of exposure to donor antigen, these findings suggest that the intraportal administration of UV-B-irradiated donor antigen works by anergic or suppressive regulatory, rather than deletional, mechanisms.

KEYWORDS

Nerve allograft - immune unresponsiveness - peripheral nerve - ultraviolet-B - portal venous injection

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