Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras

Journal Article · Fri Sep 01 04:00:00 EDT 1989 · Cellular Immunology; (USA)

DOI:https://doi.org/10.1016/0008-8749(89)90096-8· OSTI ID:5466838

Pelfrey, C M; Waxman, F J; Whitacre, C C ^[1]

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1. Ohio State Univ. College of Medicine, Columbus (USA)

Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system that has been extensively studied in the rat. The Lewis rat is highly susceptible to the induction of EAE, while the Lewis resistant (LeR) rat is known to be resistant. In this paper, we demonstrate that the LeR rat, which was derived from the Lewis strain by inbreeding of fully resistant animals, is histocompatible with the Lewis strain. Radiation chimeras, a tool for distinguishing between immunologic and nonimmunologic resistance mechanisms, were utilized to analyze the cellular mechanisms involved in genetic resistance to EAE. By transplanting bone marrow cells from LeR rats into irradiated Lewis recipients, Lewis rats were rendered resistant to EAE induction. Likewise, transplanting Lewis bone marrow cells into irradiated LeR recipients rendered LeR rats susceptible. Mixed lymphoid cell chimeras using bone marrow, spleen, and thymus cells in Lewis recipient rats revealed individual lymphoid cell types and cell interactions that significantly affected the incidence and severity of EAE. Our results suggest that LeR resistance is mediated by hematopoietic/immune cells, and that cells located in the spleen appear to play a critical role in the resistance/susceptibility to EAE induction. Depletion of splenic adherent cells did not change the patterns of EAE resistance. In vivo cell mixing studies suggested the presence of a suppressor cell population in the LeR spleen preparations which exerted an inhibitory effect on Lewis autoimmune responses. Thus, the mechanism of LeR resistance appears to be different from that in other EAE-resistant animals.

• OSTI ID: 5466838
• Journal Information: Cellular Immunology; (USA), Journal Name: Cellular Immunology; (USA) Vol. 122:2; ISSN CLIMB; ISSN 0008-8749
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL VARIABILITY
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW CELLS
CHIMERAS
CONNECTIVE TISSUE CELLS
DISEASES
GENETIC VARIABILITY
IMMUNITY
LEUKOCYTES
MAMMALS
MATERIALS
MOSAICISM
NERVOUS SYSTEM DISEASES
ORGANS
RADIATION CHIMERAS
RADIOINDUCTION
RATS
RODENTS
SOMATIC CELLS
SPLEEN
TRANSPLANTS
VERTEBRATES