Induction of autoimmunity in good and poor responder mice with mouse thyroglobulin and lipopolysaccharide.
Open Access
- 1 May 1977
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 145 (5) , 1250-1263
- https://doi.org/10.1084/jem.145.5.1250
Abstract
The administration of soluble mouse thyroglobulin (MTg) in conjunction with bacterial [Salmonella enteritidis] lipopolysaccharide (LPS) led to the termination of natural tolerance to MTg in mice. The extent of autoimmunity correlated with responsiveness to MTg, previously shown by the injection of MTg in complete Freund''s adjuvant (CFA) to be dependent upon the H-2 haplotype. In good responder B10.BR (H-2K) mice given MTg with LPS or in CFA, high antibody levels to MTg and extensive mononuclear cell infiltration in the thyroid were observed. Congenic poor responder B10.D2 (H-2d) mice given MTg plus LPS showed low levels of antibody to MTg, compared to those receiving MTg in CFA, and insignificant cellular infiltration of the thyroid. In no instance did autoimmunity develop in good or poor responder strain given MTg, LPS or CFA alone although LPS was antigenic in both of these congenic strains. Since the genetic difference in responsiveness to MTg is known to be T [thymus-derived] cell based, the involvement of T cells in LPS-treated mice was suspected. This was further ascertained by the use of athymic poor responder (BALB/c) mice and thymectomized, irradiated and bone marrow-reconstituted B10.BR mice. Antibodies to MTg were detected only in heterozygous (nu/+) mice and good responder mice reconstituted with thymus and bone marrow cells. Significant cellular infiltration in the thyroid occurred only in fully reconstituted good responder mice. The adjuvant effect of LPS on responsiveness to MTg required T cells. Since unmodified MTg and LPS abrogated self-tolerance to MTg, the need for cross-reactive T cells could be excluded. The presence of self-reactive T cells was suggested.This publication has 37 references indexed in Scilit:
- Differing responses of inbred rat strains in experimental autoimmune thyroiditisCellular Immunology, 1975
- Tolerance induction to a thymus-dependent antigen in vitro: Treatment of nonadherent cells with tolerogen biologically filtered in vitroCellular Immunology, 1974
- Autoimmune Encephalomyelitis: Activation of Thymus Lymphocytes against Syngeneic Brain Antigens in vitroScience, 1974
- FUNCTIONAL CHARACTERISTICS OF PEYER'S PATCH LYMPHOID CELLSThe Journal of Experimental Medicine, 1974
- ACTIVATION OF T AND B LYMPHOCYTES IN VITROThe Journal of Experimental Medicine, 1974
- IMMUNE RESPONSE TO A HAPTEN COUPLED TO A NONIMMUNOGENIC CARRIERThe Journal of Experimental Medicine, 1972
- Autoimmune Murine Thyroiditis Relation to Histocompatibility (H-2) TypeScience, 1971
- THE ROLE OF MYCOBACTERIA AND THE EFFECT OF PROTEOLYTIC DEGRADATION OF THYROGLOBULIN ON THE PRODUCTION OF AUTOIMMUNE THYROIDITISThe Journal of Experimental Medicine, 1969
- THE INDUCTION OF AUTOIMMUNITY IN RABBITS FOLLOWING INJECTION OF HETEROLOGOUS OR ALTERED HOMOLOGOUS THYROGLOBULINThe Journal of Experimental Medicine, 1965
- STUDIES ON THE O ANTIGEN OF SALMONELLA TYPHOSAThe Journal of Experimental Medicine, 1956