Analysis of Autoimmunity through Experimental Models of Thyroiditis and Allergic Encephalomyelitis

Weigle, William O.

doi:10.1016/s0065-2776(08)60196-0

Cited by 226 publications

(77 citation statements)

References 569 publications

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“…The amount of antigen presented to B or T cells has long been recognized as having an important bearing on both tolerance and immunity (140)(141)(142)(143)(144). Self or foreign antigens produced or administered in too small amounts either fail to induce tolerance (140)(141)(142)(143)(144), promote thymic T-cell survival instead of tolerance (145)(146)(147)(148), induce tolerance in T cells but not B cells (149), or tolerize only the higher affinity cells (27,142,149). By the same token, too little antigen can fail to trigger an immune response or selectively provide THI responses (150).…”

Section: Examples Of Tolerance By Clone Retuningmentioning

confidence: 99%

“…For B cells, abundant self antigens that are sequestered inside cells, hidden within native protein folds, or limited to extralymphoid tissues may not trigger tolerance. As a result, autoantibodies to these antigens may be more easily triggered by sudden display on dying cells (151) or exposure to immunogenic foreign antigens that happen to crossreact (144,152 (94,95). Consistent with an important proimmunity role, antibody responses are diminished when complement is depleted (88,89), deficient (90), cannot be fixed (91), or when C3d binding to CD21 is blocked (92,93 (184,185).…”

Section: Examples Of Tolerance By Clone Retuningmentioning

confidence: 99%

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Balancing immunity and tolerance: deleting and tuning lymphocyte repertoires.

Goodnow

1996

Proc. Natl. Acad. Sci. U.S.A.

415

267

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Immunological self-tolerance is ensured by eliminating or inhibiting self-reactive lymphocyte clones, creating physical or functional holes in the B- and T-lymphocyte antigen receptor repertoires. The nature and size of these gaps in our immune defenses must be balanced against the necessity of mounting rapid immune responses to an everchanging array of foreign pathogens. To achieve this balance, only a fraction of particularly hazardous self-reactive clones appears to be physically eliminated from the repertoire in a manner that fully prevents their recruitment into an antimicrobial immune response. Many self-reactive cells are retained with a variety of conditional and potentially flexible restraints: (i) their ability to be triggered by antigen is diminished by mechanisms that tune down signaling by their antigen receptors, (ii) their ability to carry out inflammatory effector functions can be inhibited, and (iii) their capacity to migrate and persist is constrained. This balance between tolerance and immunity can be shifted, altering susceptibility to autoimmune disease and to infection by genetic or environmental differences either in the way antigens are presented, in the tuning molecules that adjust triggering set points for lymphocyte responses to antigen, or in the effector molecules that eliminate, retain, or expand particular clones.

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Section: Examples Of Tolerance By Clone Retuningmentioning

confidence: 99%

Section: Examples Of Tolerance By Clone Retuningmentioning

confidence: 99%

Balancing immunity and tolerance: deleting and tuning lymphocyte repertoires.

Goodnow

1996

Proc. Natl. Acad. Sci. U.S.A.

415

267

View full text Add to dashboard Cite

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“…It is well known that tolerance states can be induced in adult animals by either simple parenteral [1,2] or oral [3] administration of soluble antigens. However, the underlying mechanisms are still not fully understood and are a subject of much current interest.…”

Section: Introductionmentioning

confidence: 99%

“…Other investigators have reported an additional immunological change in proteins due to the PEG modification; proteins could be rendered not only nonimmunogenic but also tolerogenic [18,19]. However, the necessity or benefit of the PEG conjugation of antigens to induce tolerance has been left undetermined, since, as mentioned above, unconjugated native proteins are also capable of inducing tolerance when the treatments are properly scheduled [1,2,20,21]. It is therefore important to compare the tolerogenic activity of PEG-protein conjugates with that of the native counterparts.…”

Section: Introductionmentioning

confidence: 99%

Prevention of collagen-induced arthritis (CIA) by treatment with polyethylene glycol-conjugated type II collagen; distinct tolerogenic property of the conjugated collagen from the native one

Ito¹,

Ueda

et al. 1997

Clinical and Experimental Immunology

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SUMMARYAdministration of a soluble protein into animals prior to challenge immunization induces immunological tolerance which is specific for the protein. In addition, chemical modification of proteins with polyethylene glycol (PEG) has been reported to convert the immunogenic proteins to become tolerogenic. However, differences in tolerogenic properties between PEG-modified proteins and the native counterparts have never been analysed. The ability of PEG-conjugated type II collagen (PEG-CII) to attenuate CIA, an animal model for rheumatoid arthritis, was compared with the native unconjugated CII. Groups of DBA/1 J mice were treated weekly with i.p. injections with PEG-CII, native CII, or vehicle alone for 3 weeks, before they were challenged with CII in adjuvants. The induction of tolerance was confirmed in both PEG-CII-and CII-pretreated mice when suppression of lymph node T cell proliferation in response to CII was noted. The degrees of suppression of T cell proliferation were comparable between the two pretreated groups. However, induction of arthritis and production of IgG anti-CII antibody were more markedly suppressed in PEG-CII-pretreated mice than in native CII-pretreated mice, although the severity of arthritis and antibody levels in the latter group were also lower than in control mice. IgG2a and IgG2b antibody levels were equally suppressed in the two pretreated groups, whereas the IgG1 level was significantly lower in the PEG-CII-pretreated group than in the native CII-pretreated group. The results provide the first evidence that attachment of PEG to CII renders the protein more tolerogenic.

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“…Although a major mechanism of immunologic self-tolerance is negative selection of self-reactive T cells in the thymus, experiments in the T-cell compartment have also suggested that 'receptor editing' and 'clonal anergy' are involved in tolerance induction. [2][3][4] Although these cell intrinsic processes are essential for survival of the organism, they are imperfect at times and autoreactive T cells can be found in the peripheral blood of immunologically competent animals 5 and humans. 6 To keep these potentially hazardous autoreactive T cells under control, the immune system has evolved an extrinsic form of dominant tolerance which involves regulatory T cells (Tregs).…”

Section: Introductionmentioning

confidence: 99%

Regulating regulatory T cells

Chao

2006

Bone Marrow Transplant

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Analysis of Autoimmunity through Experimental Models of Thyroiditis and Allergic Encephalomyelitis

Cited by 226 publications

References 569 publications

Balancing immunity and tolerance: deleting and tuning lymphocyte repertoires.

Balancing immunity and tolerance: deleting and tuning lymphocyte repertoires.

Prevention of collagen-induced arthritis (CIA) by treatment with polyethylene glycol-conjugated type II collagen; distinct tolerogenic property of the conjugated collagen from the native one

Regulating regulatory T cells

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