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Review
. 2001 Sep 3;194(5):F31-6.
doi: 10.1084/jem.194.5.f31.

Organ-specific autoimmune disease: a deficiency of tolerogenic stimulation

S Lesage  1 , C C Goodnow
Affiliations
Review

Organ-specific autoimmune disease: a deficiency of tolerogenic stimulation

S Lesage et al. J Exp Med. .
No abstract available

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Figures

Figure 1
Figure 1
Immunogenic and tolerogenic roles of B7 ligands are context dependent. B7 ligands promote induction of T cell tolerance when antigens are presented chronically and/or early during thymic development. In the context of antigens presented as an acute burst—during an immune response to invading pathogens—B7 ligands play an immunogenic role promoting T cell expansion and effector functions.
Figure 2
Figure 2
Models to account for autoimmunity differences among congenic NOD mouse strains. (A) Enhancement of immunogenic APCs in draining lymph nodes or within target organ. MHC II and B7-2 stimulate T cell reactivity to islet antigens, and B7-1 enhances autoimmunity to PNS antigens. In this model, deletion of B7-2 would suppress diabetes by diminishing immunogenic stimulation by islet antigens, and would trigger autoimmune neuropathy by a compensatory increase in B7-1 on immunogenic APCs. Autoimmunity is not seen in B7-2 knockout B6 mice due to a less efficient MHCII allele and absence of other immunogenic costimuli caused by non-MHC NOD gene alleles. It is difficult to explain the enhanced autoimmunity in NOD.CD28−/− mice by this model. (B) Diminished presentation of antigens by tolerogenic APCs. In this model, islet and neural antigen presentation is reduced by NOD MHC II, diminishing induction of tolerant T cells and promoting diabetes. B7-2 is suggested to be the predominant molecule on tolerogenic APCs presenting neural antigens in the thymus or peripheral nodes, so that its elimination selectively diminishes tolerance induction to these antigens. By contrast, B7-1 may be the predominant member on tolerogenic APCs bearing islet antigens, so that diabetes is exaggerated when it is inactivated, or when both costimulators or CD28 are eliminated. For spontaneous autoimmunity to occur, other NOD gene alleles are needed to further weaken tolerogenic responses at the level of tolerogenic APC numbers and by intrinsically diminishing the T cell response to tolerogenic stimuli.
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Comment on

References

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