Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Experimental acute adult T cell leukemia-lymphoma is associated with thymic atrophy in human T cell leukemia virus type I infection.
Lab Invest. 1996 Mar;74(3):696-710. Unique Identifier : AIDSLINE MED/96175627 Simpson RM; Zhao TM; Hubbard BS; Sawasdikosol S; Kindt TJ; Laboratory of Immunogenetics, National Institute of Allergy and; Infectious Disease, National Institutes of Health, Rockville,; Maryland, USA.
Abstract:
Human T cell leukemia virus type I (HTLV-1) infection may lead to an acutely fatal adult T cell leukemia-lymphoma (ATLL), but HTLV-1-infected people usually remain asymptomatic. Why only certain HTLV-I infections lead to acute ATLL, which is characterized by leukemic infiltration of multiple organs and immune suppression, remains unknown. A readily accessible animal model in which the spectrum of consequences resulting from HTLV-I infection can be observed would greatly aid studies of this retrovirus. New Zealand White rabbits inoculated with either HTLV-1-infected CD25+ T cells or cell-free virus, were serially necropsied at different intervals after death or humane sacrifice. Tissues were preserved at necropsy or cultured in vitro and subsequently prepared for morphologic or molecular examination. Rabbits inoculated with RH/K34, a productively infected rabbit T cell line that contains a monoclonally integrated full-length HTLV-I provirus, developed acute ATLL-like biologically malignant lymphoproliferative disease with lymphocyte infiltration of viscera; lymphomas consisting primarily of monoclonal expansions of RH/K34 manifested a variety of diffuse pleomorphic histologic types. Concurrently, lymphoproliferative disease was associated with onset of thymic atrophy in the presence of rapidly increasing thymic proviral load. In contrast, rabbits given two other HTLV-1 inocula, originally derived (as was RH/K34) using the human T cell line MT-2 as virus source, also became infected but did not develop thymic atrophy or the ATLL-like disease. HTLV-1 infection, thymic atrophy, and leukemic infiltration similar to acute ATLL occurred reproducibly in a New Zealand White rabbit model independent of RH/K34 inoculum and host histocompatibility. Thymic atrophy in RH/K34-inoculated rabbits, but not in rabbits given other similar HTLV-1, was consistent with immunosuppression sufficient to prevent rejection of the inoculum. Although the short, 8-day course of the experimental ATLL precludes its having a molecular pathogenesis identical to the human condition, the systemic consequences of acute ATLL, including its association with thymic atrophy, are closely modeled.
Keywords: Adult Animal Disease Models, Animal Female Human HTLV-I/PATHOGENICITY HTLV-I Infections/*COMPLICATIONS/IMMUNOLOGY/*PATHOLOGY Immunogenetics Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/*ETIOLOGY/ IMMUNOLOGY/*PATHOLOGY Lung/PATHOLOGY Lymph Nodes/IMMUNOLOGY/PATHOLOGY Major Histocompatibility Complex Rabbits Spleen/IMMUNOLOGY/PATHOLOGY T-Lymphocytes/IMMUNOLOGY/PATHOLOGY Thymus Gland/IMMUNOLOGY/*PATHOLOGY JOURNAL ARTICLE 960730
M9670503
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
