Tolerance-Mediated Inheritance of Immune Responsiveness

Cinader, B.; Koh, Sean; Naylor, D.H.

doi:10.1159/000230168

Cited by 13 publications

(4 citation statements)

References 18 publications

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“…One is that a gene product ofthe H-2D allele cross-reacts with the antibody combining specificity ofthe F molecule, thereby inducing selftolerance at the B-cell as well as the T-cell level (for that matter, this product may cross-react with the carrier portion of the molecule so the nonresponder possesses both carrier types on [possibly] its spleen cells) . Such dominant nonresponsiveness mediated by a tolerance mechanism would be similar to that described by Cinader et al (7) for the inheritance of immune responsiveness to complement component C-5.…”

Section: Discussionsupporting

confidence: 73%

Dominant nonresponsiveness in the induction of autoimmunity to liver-specific F antigen.

Silver¹,

Lane²

1975

The Journal of Experimental Medicine

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The liver-specific F antigen, although not an autoimmunogen, can induce the production of autoantibodies in responder strains. The ability to respond is under the control of two genes, one linked to the H-2 locus of mice, the other not. Responders possessing both genes produce high anti-F titers, while the H-2-linked gene alone permits a significant but low antibody response. (Responder X nonresponder) F1 hybrids derived from parents possessing identical F molecules are nonresponders, in contrast with the dominance of responsiveness in Ir gene systems. The presence of the H-2 locus from nonresponders appears involved in the inability to respond. This is discussed in terms of self-tolerance and suppression.

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Section: Discussionsupporting

confidence: 73%

Dominant nonresponsiveness in the induction of autoimmunity to liver-specific F antigen.

Silver¹,

Lane²

1975

The Journal of Experimental Medicine

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“…Thus, the helper T cells from C5-(OSN) mice were not rendered unresponsive in a host that contained T, cells and the antigen in its native physiologic form. This is consistent with the suggestion of Cinader et al that C5 induces tolerance in young but not in adult mice [17].…”

Section: Discussionsupporting

confidence: 94%

Mice naturally tolerant to C5 have T cells that suppress the response to this antigen

1986

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We examined whether C5-sufficient mice which are naturally tolerant to this antigen have suppressor T cells to C5 humoral immune response. Two congenic strains of mice B10.D2 (NSN) and B10.D2 (OSN) differing only in the presence or absence of C5 were used. Irradiated (760 rds) sufficient hosts were reconstituted with a nonadherent spleen cell suspension from either sufficient or deficient mice or a mixture of both. Hemolytic C5 levels were assayed. Sufficient spleen cells appeared to prevent the drop of C5 level caused by anti-C5 antibody made by deficient spleen cells. Spleen cell suspensions from sufficient mice primed with deficient spleen cells exhibited better anti-C5 activity than normal sufficient spleen cell suspensions. This anti-C5 activity is abrogated by treatment of the NSN spleen cell suspensions obtained from NSN primed with OSN spleen cells with anti-Thy-1.2 antiserum and complement. Suppression of the humoral response to C5 failed to affect the anti-sheep red blood cell immune response. Suppressor T cells are resistant to low-dose irradiation, cortisone treatment and adult thymectomy. In contrast, they are sensitive to high doses of irradiation and both high and low doses of cyclophosphamide treatment. Thus, C5-sufficient mice, in contrast to C5-deficient mice, appear to have antigen-specific suppressor T cells which downregulate the humoral immune response to C5. In addition, we examined the relationship of these suppressor T cells to the state of tolerance in helper T cells of C5-sufficient mice. This was done in irradiated deficient mice which were repopulated with spleen cell suspensions selectively depleted of either Lyt-1+ or Lyt-2+ T cell subsets. These chimeras were challenged with murine C5 and both the primary and secondary immune response was measured by inhibition of the C5 hemolytic activity. It was found that only spleen cell suspensions of the deficient mice selectively depleted from the Lyt-2+ subset of T cells responded to the antigen both in the primary and secondary response. In contrast, either subset of T cells from the sufficient mice failed to respond. Thus, it appears that in sufficient mice helper T cells to C5 are intrinsically tolerant or physically and/or functionally deleted. In conclusion, the data suggest that both T cell compartments are unresponsive and play a role in the mechanism of tolerance to a physiologic antigen.

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“…Except for the copolymer L-glutamic acid50-L-tyrosine50 (GT), these involve responses to alloantigens or altered-self proteins. These include the antibody responses to Ea-1 (20), the complement component C-5 (10), the F liver antigen (35), GT (16), Thy-1.2 (42), trinitrophenyl-conjugated mouse serum albumin (37), dinitrophenyl-conjugated bovine gamma globulin (9), trinitrophenyl-conjugated human serum albumin (9), and sheep erythrocytes (9,23), as well as the T-cell proliferative response to GT (16). The antifimbria system described here is the only one in which dominant low responsiveness to a functional protein antigen from a bacterium has been described.…”

Section: Discussionmentioning

confidence: 99%

Genetic control of serum antibody responses of inbred mice to type 1 and type 2 fimbriae from Actinomyces viscosus T14V

et al. 1991

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Antibodies reactive with type 1 and type 2 fimbriae from Actinomyces viscosus T14V specifically inhibit the adherence of A. viscosus T14V to salivary pellicle-coated tooth surfaces and other bacteria, and these antibodies are thought to modulate colonization by this microorganism. These studies were done to determine whether previously noted differences in the antibody responses of inbred mice to type 1 and type 2 fimbriae might be under genetic control. The serum immunoglobulin G (IgG) and IgM antibody responses of inbred, F1 hybrid, and H-2 congenic mice, immunized with A. viscosus T14V cells, were analyzed by enzyme-linked immunosorbent assays for antibodies reactive with A. viscosus T14V whole-cell type 1 and type 2 fimbriae. The results confirmed earlier findings and indicated striking variations in the amounts of IgG anti-type 1 (23-fold) and anti-type 2 (48-fold) fimbria antibodies elicited. The responses of the 17 inbred strains tested showed a relatively continuous distribution from high to low, as well as marked differences in the responses of H-2 and Igh-C identical strain pairs. An analysis of the responses of F1 hybrid and H-2 congenic mice indicated dominance of the low-responder gene(s) and control by H-2-linked genes. Antisera from two high-responder strains inhibited in vitro bacterial adherence to a much greater degree than antisera from a low-responding strain. These data suggest polygenic control of the magnitude of the IgG anti-type 1 and anti-type 2 fimbria antibody responses by H-2-linked genes as well as background genes not associated with H-2 or Igh-C loci.

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Tolerance-Mediated Inheritance of Immune Responsiveness

Cited by 13 publications

References 18 publications

Dominant nonresponsiveness in the induction of autoimmunity to liver-specific F antigen.

Dominant nonresponsiveness in the induction of autoimmunity to liver-specific F antigen.

Mice naturally tolerant to C5 have T cells that suppress the response to this antigen

Genetic control of serum antibody responses of inbred mice to type 1 and type 2 fimbriae from Actinomyces viscosus T14V

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