Quantitative Studies on the Induction of Tolerance of Skin Homografts and on Runt Disease in Neonatal Rats2

Abstract

Two highly inbred but unrelated strains of rat, Lewis and B.N., were used in quantitative studies to determine the influence of dose, histological origin, and time of intravenous injection after birth of living homologous cell inocula on the induction of 1) tolerance of subsequent skin homografts and 2) runt disease in this species. Cell dose was an important factor in induction of tolerance and must be considered in any definition of the tolerance-responsive period. Evidence is presented that cell suspensions derived from different components of the lympho-hematopoietic system differ in their capacity to confer tolerance in respect to skin. F₁ hybrid bone marrow cells were as effective in conferring tolerance as parental-strain marrow cells, but spleen cells, node cells, and leukocytes from adult hybrid donors gave significantly inferior results. However, spleen cells from infant donors were as effective as adult marrow cells. Parental-strain thymocytes were just perceptibly effective. The evidence suggests that tolerance may be induced by cells of some types in respect to themselves which does not extend to skin homografts of similar genetic origin. Thus, there may be differences between the spectra of transplantation antigens expressed by different types of tissue cells from the same individual. Depending on the dose administered, cellular inocula derived from adult spleens, lymph nodes, thoracic-duct lymphocytes, and leukocytes all caused runt disease, though thymocytes were relatively harmless even at high dose levels. Induction of a demonstrable level of tolerance is not necessary for development of this condition. The clinical history and pathology of runt disease was analyzed. In young rats, this disease is characterized by the arrest of body growth, diffuse dermatitis, enlargement of spleen and lymph nodes, with follicular atrophy, atrophy of the thymus, dyscrasia of bone marrow and blood, and hypothermia. Development of these symptoms follows a definite sequence, and death occurs within 15 to 22 days after inoculation of the homologous, immunologically competent cells. Possible pathogenesis of runt disease is discussed, though no completely satisfactory interpretation of the syndrome can be given. An attempt is made to differentiate primary symptoms, resulting from the immunological reaction of the grafted tissue against the host, from secondary ones.