Mls and Tolerance

Festenstein, H; Kumura, Shoji; Blasi, Glovanni

doi:10.1111/j.1600-065x.1989.tb00002.x

Cited by 16 publications

(12 citation statements)

References 69 publications

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“…MIs determinants, which have been found only in mice at present, are non-MHC gene products expressed by antigen-presenting cells including B cells (Sunshine et al, 1985;Webb et al, 1989;Molina et al, 1989). A very high proportion of T cells from Mls1b mice shows the ability to respond to leucocytes expressing the Mls-la (Festenstein, Kumura & Biasi, 1989). It has been postulated that the TcR repertoire is shaped by both negative selection (Nossal, 1983) and positive selection (Zinkernagel & Doherty, 1979) in association with MHC antigens, although the cellular and molecular basis of repertoire selection remains unclear.…”

Section: Resultsmentioning

confidence: 99%

Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence strain, BALB/c, and a low-incidence strain, DBA/2

Mori

Hosono²,

Murakami

et al. 1991

Clinical and Experimental Immunology

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SUMMARYThymectomy on day 3 after birth induced autoimmune gastritis (AIG) at the age of 2 months in 51-73% of BALB/c mice, and in only 3-5% of DBA/2 mice. AIG was detected by histological and serological (immunofluorescence staining for detecting anti-parietal cell autoantibody) examination. However, autoantibody was weakly positive in almost all of these DBA/2 mice when measured by ELISA using extract of murine gastric mucosa as the antigen. To investigate genetically the mechanism controlling the incidence of AIG, 11 recombinant inbred strains established by brothersister mating of (BALB/c x DBA/2) F2 mice (C x D2 strains) were used. Among 26 markers tested, the Mls-locus on BALB/c chromosome I and the Hc locus coding a complement component (C5) on BALB/c chromosome 2 were found to be associated with high susceptibility to AIG. However, if one or both of the loci were of DBA/2 origin, mice showed medium or low susceptibility to AIG. For further analysis, F I, F2 and back-cross generations of these two strains were tested, but segregation of a single susceptibility or insusceptibility gene was not obtained. Taken together, it seems probable that two or more genes are involved in the induction mechanism of AIG. We did not detect C5 deposition in AIG lesions, nor complement-dependent cytotoxic antibody to parietal cells in serum from AIG mice. However, injection of irradiated spleen cells of DBA/2 mice into BALB/c mice thymectomized on day 3 augmented the incidence ofAIG from 71 to 100%, but not that of oophoritis (33%). A relationship between Mls-la determinants and the pathogenesis of AIG was further suggested from the fact that V.6 TcR-expressing T cells increased in number in AIG-bearing compared with normal BALB/c mice.

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Section: Resultsmentioning

confidence: 99%

Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence strain, BALB/c, and a low-incidence strain, DBA/2

Mori

Hosono²,

Murakami

et al. 1991

Clinical and Experimental Immunology

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“…Thymocytes bearing Vp8.1 and Vp6 TCR are normally eliminated in mice expressing MIs-a, whereas Vp3 TCR+ cells are eliminated from mice expressing Mls-2a (12)(13)(14)(15). Although the Mls genes and products are unknown, Mls is the only other endogenous antigen besides the MHC molecules that is able to stimulate in vitro proliferation of a high proportion ofT cells from unimmunized Mls-mice (30). Mls antigens appear to differ from conventional antigens in that they can be presented by most MHC molecules (31), especially class II I-E; however, there appears to be a hierarchy in the efficiency ofMls presentation by the different mouse MHC haplotypes, in that H-2k, H-2d > H-2b > H-2q (12).…”

Section: Tolerance By Clonal Deletionmentioning

confidence: 99%

Clonal Deletion Versus Clonal Anergy: The Role of the Thymus in Inducing Self Tolerance

Ramsdell

Fowlkes

1990

Science

351

138

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During development in the thymus, T cells are rendered tolerant to self antigens. It is now apparent that thymocytes bearing self-reactive T cell receptors can be tolerized by processes that result in physical elimination (clonal deletion) or functional inactivation (clonal anergy). As these mechanisms have important clinical implications for transplantation and autoimmunity, current investigations are focused on understanding the cellular and molecular interactions that generate these forms of tolerance.

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“…At the same time analysis of the minor lymphocyte stimulatory (Mls) system provided insights into general aspects of T-cell recognition and repertoire generation (reviews in Abe and Hodes, 1989;Festenstein et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Regulatory T cells in the establishment and maintenance of self-tolerance: role of the thymic epithelium

Salaün¹,

Corbel²,

LeDouarin³

2005

Int. J. Dev. Biol.

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The thymus constitutes the microenvironment for T lymphocyte differentiation and acquisition of self-tolerance. Aiming to specify the contributions of the two essential parts of the thymus, namely hemopoietic and epithelial, we have devised experimental models in birds and mice. Chimeric thymuses, xenogeneic in birds and allogeneic in mice, were constructed early in development. In both models we could demonstrate a critical role of the epithelial component of the thymic stroma in induction and maintenance of self-tolerance. These experiments showed that suppression mechanisms are also implicated in these events, strongly suggesting the existence of regulatory T cells in both models. Before these experiments the control of selftolerance was usually attributed to suppressive cells. However, as the cell phenotypes were not identified, the role of these cells was disregarded. Numerous studies since our investigations argue in favour of regulatory mechanisms. The work we initiated several years ago represents a contribution to our understanding of the two linked and opposite aspects of immune-responded control, namely self-tolerance and autoimmunity.

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Mls and Tolerance

Cited by 16 publications

References 69 publications

Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence strain, BALB/c, and a low-incidence strain, DBA/2

Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence strain, BALB/c, and a low-incidence strain, DBA/2

Clonal Deletion Versus Clonal Anergy: The Role of the Thymus in Inducing Self Tolerance

Regulatory T cells in the establishment and maintenance of self-tolerance: role of the thymic epithelium

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