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Biomedical subjects

W S Lapp

Publications and source records attributed to W S Lapp.

At least 73 records · Page 4Linked to original sources

Thymic epithelial injury in graft-versus-host reactions following adrenalectomy.

In four separate experiments 140 adults A(H-2a) x C57BL/6(H-2b) F1hybrid mice were surgically adrenalectomized and divided into three experimental groups. Seventy-one additional adult F1hybrids (AXC57BL/6) which had not been adrenalectomized were divided into three similar groups. In Group 1 (GvH group), GvH reactions were induced by the injection of 50 x 106 pooled parental lymphoid cells intravenously. The second group (syngeneic group) received 50 x 106 pooled F1 hybrid lymphoid cells intravenously. The third group (uninoculated group) received no lymphoid inoculum. At regular intervals the animals were killed, autopsied, and histologically studied. Visceral alterations of GvH reaction were recorded in the thymus, lymph nodes, spleen, and liver in the GvH groups; none was present in the other groups. The thymuses in the nonadrenalectomized GvH group underwent prompt involution characterized by size reduction and cortical lymphoid cell depletion. These changes were not apparent in the GvH adrenalectomized group. Both GvH groups, however, demonstrated an effacement of the medulla, lymphocyte incursion into the medulla, lymphocyte emperipolesis of medullary epithelial cells, gradual disappearance of Hassall's corpuscles, epithelial cell injury, and an ingress of macrophages laden with nuclear and cellular debris. This study suggests that the stress and corticosteroid response which accompany a GvH reaction account for the reduction in the thymic size and cortical lymphoid cell mass. The medullary alterations, therefore, would appear to be initiated by the GvH reaction per se.

Adrenal Glands↗

Thymic involution in murine graft-versus-host reaction. Epithelial injury mimicking human thymic dysplasia.

Mild, moderate, and severe graft-versus-host (GVH) reactions were induced in four series of experiments in 71 CBA X A and C57BL/6 X A F1 hybrid mice. At regular intervals post-GVH reaction induction (Days 4-42), the animals were sacrificed, autopsied, and histologically studied. Visceral alterations of GVH reaction were recorded in the spleen, lymph nodes, liver, kidney, gut, and thymus. A spectrum of thymic changes was documented, ranging from obliteration of a definable cortex and medulla with loss of Hassall's corpuscles to marked involution with complete disappearance of the gland. Ultrastructural studies revealed damage to both lymphocytes and epithelial cells along with lymphocyte emperipolesis of epithelial cells, lymphocytolysis within epithelial cells, and accumulation of numerous autophagic vacuoles containing fragments of cellular debris within epithelial cells and histiocytes. The resemblance of these alterations to human thymic dysplasia as observed in primary immunodeficient conditions was striking. The theoretical implications of these studies for the pathogenesis of human congenital immunodeficiency states are considered.

Animals↗

Experimental stimulation of cell-mediated immunity without concomitant stimulation of humoral immunity in graft-versus-host immunosuppressed mice.

The immunosuppressive effect of the graft-versus-host (GVH) reaction was studied in CBA X A F1 (CAF1) mice which had been rendered immunologically unresponsive by the injection of parental A strain lymphoid cells (GVH mice). Suppression of both cell-mediated and humoral immune responses was demonstrated by the prolonged survival of C57BL/6 (B6) skin allografts and by the inability of GVH mice to produce detectable antibody following stimulation with sheep erythrocytes (SRBC). Appropriate stimulation of GVH mice induced cell-mediated immune reactions to xeno- and allogeneic antigens while the humoral immune responses to the same antigens remained suppressed. Multiple challenges of the GVH mice with B6 tissue caused a rapid rejection of subsequent B6 skin grafts but failed to stimulate the production of any detectable antibodies to B6 allotransplantation antigens. Sensitization of GVH mice with SRBC in Freund's complete adjuvant stimulated a delayed hypersensitivity response to SRBC, although no humoral response to SRBC could be detected, even after three challenges with SRBC. The experimental results are discussed in terms of a proposed model for GVH-induced immunosuppression.

Animals↗