MORPHOLOGICAL-STUDIES ON AVIAN SPINAL-CORD CHIMERAS

Spinal cord chimeras were constructed by orthotopic grafting of quail embryonal neutral folds, neural crest and neural tube into chicken emb ryos. The spinal cord xenografts were accepted for varying lengths of time, but most chimeras eventually rejected the quail transplant. This was associated with perivenular cuffing and demyelination with preser vation of most neurons, as well as clinical neurological symptoms. Twe nty-four chimeras were studied to delineate the time of first appearan ce of glial deposits of immunoglobulin and to identify the subpopulati ons of T cells in spinal cord infiltrates. The results suggested that deposits of immunoglobulins on glial elements preceded inflammatory ce ll infiltration. The perivenular cuffs consisted predominantly of T ce lls and showed a preponderance of CD8- over CD4-positive cells (CD4/CD 8 ratios around 0.6). Further, CD4+ cells were found almost exclusivel y in the central portions of the infiltrate, with the periphery consis ting almost only of CD8+ cells. The diffuse cellular infiltrate of the parenchyme contained T and plasma cells. The T cells were almost excl usively CD8+. Plasma cells were seen only at the outer borders of the cuffs and dispersed throughout the quail-derived spinal cord tissue. I t seemed that rejection of quail-derived melanocytes in feathers ('qua il-like feathers'), described by us earlier, often preceded neurologic al symptoms and showed a histopathological pattern comparable to spina l cord lesions, i.e., predominantly perivascular cuffing. In prelimina ry studies, enhancement of disease by immunization with quail organ su spension and decreased intensity of disease by combined immunosuppress ive treatment with FK 506 and cycylophosphamide were suggested, The da ta presented here are compatible with the hypothesis that rejection of CNS quail tissue by chimeras is preceded in the periphery by rejectio n of melanocytes in segments of skin and in feathers, and that the spi nal cord rejection relies on xenoantibodies and on cytotoxic as well a s delayed hypersensitivity type T cells. Finally, these data strengthe n the analogy between the histopathologic presentation and immune effe ctor composition of the xenograft rejection lesions in the chimeras an d the plaques seen in patients with multiple sclerosis.