J. Wayne Streilein M.D.¹ and R. E. Billingham F.R.S¹

¹ From the Departments of Medical Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

F₁ hybrid hamsters derived from genetically disparate strains develop a severe and often lethal cutaneous disorder when inoculated intracutaneously with immunologically competent lymphoid cells from either parental strain, The disease is characterized clinically by extensive epidermal necrolysis, and histologically by a complete dissolution of the dermal-epidermal junction. The requisites for elicitation of this syndrome were determined to be: (a) the parental strains must differ from each other at a major histocompatibility locus, and (b) the donor inoculum must contain immunologically competent parental strain cells. In addition it was found that specifically sensitized cells surpassed normal unsensitized ones in their ability to elicit the disease, and that the disease can be transferred adoptively from affected to normal F₁ hosts by means of lymphoid cells. On the basis of these observations, it was concluded that the disease was immunologic in nature, and graft-versus-host in type. However, a series of critical studies failed to demonstrate that the epidermolysis had an immunogenetically specific basis, thus invalidating the provisional assumption that this lesion resulted from a direct immunologic attack upon parenchymal cells of the epidermis and dermis. With the aid of radiation chimeras, it was clearly established that typical epidermolysis could be induced in skin of the same genetic constitution as the attacking donor lymphoid cells. This paradox was taken into account by the possibility that, amid the intense local cutaneous graft-versus-host reactions, "skin-specific" antigenic determinants are bared which incite a quasi autoimmune response that in turn is responsible for the epidermolytic lesions.

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