Production of Runt Disease in Tolerant Mice by the Injection of Syngeneic Lymphoid Cells

Abstract

When chimeric A strain mice tolerant of (A x C57BL/1)F1 hybrid skin grafts are injected with spleen cells from normal A donors the recipients develop weight loss, clinical evidence of runting, and death in some animals. Similar recipients injected with spleen cells from A strain donors immunized against C57BL/1 tissue show a more rapid onset of the runting process and increased mortality. Runting in. these experiments therefore results from an immune attack by the injected A strain lymphoid cells against the (A x C57BL/1)F1 hybrid tissue harbored by the chimeric recipients. Since the hybrid tissues of the chimeric recipients were derived from spleen cell populations we conclude that the immunologic rejection of lymphoid and hematopoietic tissue is sufficient to cause the runting syndrome. C3H mice tolerant of A strain skin grafts because of the prior injection of viable or disrupted A strain spleen material were given 400 r of x-irradiation and an injection of C3H spleen cells. Only the chimeric C3H mice harboring viable A strain cells developed weight loss and clinical evidence of disease, showing again that runting occurs only when an attack can be made against viable lymphoid and hematopoietic tissue. Normal A strain mice injected intravenously with 850 million (A x C57BL/1)F1 hybrid spleen cells reject hybrid skin grafts and do not develop runting, whereas the rejection of similar hybrid tissue present in chimeric A strain mice results in runting. It is concluded that runting will occur only when the immunologic attack is directed against lymphoid and hematopoietic tissue which has become established within host tissues. The possibility that runting may result from hypersensitivity reactions occurring in the lymphoid tissues is discussed.

Immunologic deficiency, autoimmune disease, and lymphoma: Observations, implications, and speculations

“…First, neonatally thymectomized animals are immunological-uImmunologic attack on lymphoid and hematopoietic tissues in the absence of attack against other tissues appears sufficient to cause graftversus-host disease. 12 {Runt disease may also be produced by injection of immunologically competent foreign cells into lethally irradiated adult mice13 and by treatment of newborn mice with cortisol acetate.14 Presumably both of these maneuvers result directly or indirectly in a diminution of host lymphoid celb and immunologic competence. ly deficient.…”

Pathogenesis of Graft-versus-Host Reaction

“…Although the etiology of the syndrome is widely accepted and patho logical studies of animals suffering from graft-versus-host reaction arc numerous, the pathogenesis of the reaction is not clearly understood [3,4,15,23]. This is partly because of the complexity of the changes and the inability to separate the primary and secondary changes [4].…”

“…In order for a graft-versus host reaction to occur, certain conditions must be present: (1) the injected cells must be immunologically competent; (2) the recipient must be unable to reject the injected cells; (3) the host must possess antigens that are absent from the donor cells. This phe-H kim/Y unis/G ood nomenon has been studied utilizing newborn mice [2|, adult mice pre viously rendered tolerant of the donor antigens [18], adult mice immunologically paralyzed by irradiation [22], first filial generation hybrid mice which are genetically tolerant of parental strain antigens [7], and in chimeric animals syngeneic with the cell donor strain [15], The syn drome that develops has been given a variety of names, such as runt disease, homologous disease and secondary disease, depending upon conditions of induction.…”