Tolerance to Thyroglobulin by Activating Suppressor Mechanisms *

Kong, Yi‐chi M.; Okayasu, Isao; Giraldo, Alvaro A.; Beisel, Kirk W.; Sundick, Roy S.; Nr, Rose; David, Chella S.; Audibert, F.; Chedid, L

doi:10.1111/j.1749-6632.1982.tb36108.x

Cited by 75 publications

(69 citation statements)

References 22 publications

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“…Kong et al [2] first published data showing that EAT could be prevented by prior injection of soluble MTg i.v. These authors also showed that the induced suppression was transferable with SC, and that T rather than B cells were the active cell population.…”

Section: Discussionmentioning

confidence: 97%

“…Kong et al. [2] showed that development of EAT could be suppressed if animals were first injected with soluble MTg i.v. In a previous report we described the conditions we found to be necessary for consistent induction of tolerance to MTg and our inability to break this tolerance by immunizing with xenogeneic Tg or hapten-substituted syngeneic Tg [3].…”

Section: Introductionmentioning

confidence: 98%

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Phenotypic characteristics of cells involved in induced suppression to murine experimental autoimmune thyroiditis

1988

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Suppression of induced experimental autoimmune thyroiditis can be consistently transferred with spleen cells to syngeneic recipients, provided they are first treated with 200 rads irradiation. Treatment with anti-Thy-1 in vivo immediately prior to transfer abrogates the suppression, while depleting B cells has no effect. The in situ induced tolerance can be prevented by treatment with monoclonal antibodies to the Ly-1 or L3T4 molecules either prior to or post tolerization. Anti-Ly-2 treatment has no effect. In the transfer, again treatment of donors with anti-L3T4 prior to transfer prevents the demonstration of suppression in the recipients, while anti-Ly-2 does not affect suppression. These data suggest that the suppression is being mediated either by a CD4+ T suppressor cell or a CD4+ suppressor inducer cell. Preliminary experiments do not support the possibility of a CD8+ suppressor cell being activated in the recipient.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Phenotypic characteristics of cells involved in induced suppression to murine experimental autoimmune thyroiditis

1988

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“…For example, human HLA-DRB1*0301 (DR3) transgene (27) and murine H2 k (CBA/J) confer susceptibility to autoimmune thyroiditis, whereas murine H2 autoimmune thyroiditis is also characterized by mononuclear cell infiltration, autoantibody production, and T-cell proliferation. Susceptible mice can be tolerized to mTg by short-term elevation of circulating mTg (31). This induced tolerance is abrogated by depletion of CD25 + cells and mice again become susceptible to experimental autoimmune thyroiditis (24).…”

Section: Cd4mentioning

confidence: 99%

Concurrent Induction of Antitumor Immunity and Autoimmune Thyroiditis in CD4+CD25+ Regulatory T Cell–Depleted Mice

et al. 2005

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When CD4 + CD25 + regulatory T cells are depleted or inactivated for the purpose of enhancing antitumor immunity, the risk of autoimmune disease may be significantly elevated because these regulatory T cells control both antitumor immunity and autoimmunity. To evaluate the relative benefit and risk of modulating CD4 + CD25 + regulatory T cells, we established a new test system to measure simultaneously the immune reactivity to a tumor-associated antigen, neu, and an unrelated self-antigen, thyroglobulin. BALB/c mice were inoculated with TUBO cells expressing an activated rat neu and treated with anti-CD25 monoclonal antibody to deplete CD25 + cells. The tumors grew, then regressed, and neu-specific antibodies and IFN-;-secreting T cells were induced. The same mice were also exposed to mouse thyroglobulin by chronic i.v. injections. These mice produced thyroglobulinspecific antibody and IFN-;-secreting T cells with inflammatory infiltration in the thyroids of some mice. The immune responses to neu or thyroglobulin were greater in mice undergoing TUBO tumor rejection and thyroglobulin injection than in those experiencing either alone. To the best of our knowledge, this is the first experimental system to assess the concurrent induction and possible synergy of immune reactivity to defined tumor and self-antigens following reduction of regulatory T cells. These results illustrate the importance of monitoring immune reactivity to self-antigens during cancer immunotherapy that involves immunomodulating agents, and the pressing need for novel strategies to induce antitumor immunity while minimizing autoimmunity. (Cancer Res 2005; 65(18): 8471-8)

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“…Perhaps the most apposite finding is that T cell-mediated suppression of experimental autoimmune thyroiditis is evoked by injection of large doses (> 100 pg i.v.) of soluble mouse thyroglobulin [14]. In fact thyroglobulin and F protein behave in much the same way as immunogens, except that thyroglobulin clearly purges the Th compartment less effectively; otherwise it would not be able to elicit experimental autoimmune disease.…”

Section: Discussionmentioning

confidence: 92%

Self‐ and allo‐specific suppressor T cells evoked by intravenous injection of F protein

Lukic

1984

Eur J Immunol

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The liver/serum protein F appears to inactivate clones reactive towards itself in the T helper cell but not the B cell compartment. To examine the extent of self-reactivity in the T suppressor cell compartment, the well-established procedure of i.v. injecting milligram doses of the protein was used. To detect suppression, an entirely in vitro proliferation assay was devised, based on use of immunopurified F antigen. In this way T suppressor cells could be detected after activation either by allogeneic F, or (though to a lesser extent) by self-F protein. Thus the T suppressor cell compartment contains potentially self-reactive clones, and to that extent the receptor repertoire of T suppressor cells overlaps with B rather than T helper cells.

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Tolerance to Thyroglobulin by Activating Suppressor Mechanisms *

Cited by 75 publications

References 22 publications

Phenotypic characteristics of cells involved in induced suppression to murine experimental autoimmune thyroiditis

Phenotypic characteristics of cells involved in induced suppression to murine experimental autoimmune thyroiditis

Concurrent Induction of Antitumor Immunity and Autoimmune Thyroiditis in CD4+CD25+ Regulatory T Cell–Depleted Mice

Self‐ and allo‐specific suppressor T cells evoked by intravenous injection of F protein

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