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Autoimmunity

The pathogen connection

Nature volume 394, pages 227–228 (1998)Cite this article

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Several indirect arguments support the idea that microbial agents influence the occurrence or course of certain autoimmune diseases. These include the fact that migrant populations acquire the disease prevalence of the geographical area to which they move, a prevalence correlated with latitude; that the incidence or frequency of autoimmune diseases has dramatically changed in the last two centuries; and that non-obese-diabetic (NOD) mice are protected from diabetes by bacterial infections. The nature of the agents involved and their mechanism of action remain unclear. Is there immunological cross-reactivity between anti-pathogen and anti-self responses — molecular mimicry? Or do the pathogens upset the metastable equilibrium of self-tolerance by disrupting immunoregulation — bystander activation? Recent papers1,3, the latest by Horwitz et al.1 in this month's Nature Medicine, bring interesting evidence to the debate.

Immune tolerance to self is not absolute. Given the breadth of protein epitopes in higher eukaryotes, an immune system from which all potential self-reactivity had been deleted would probably not respond to anything. Thus, clonal deletion in the thymus and peripheral lymphoid organs seems to spare a large number of T lymphocytes that are potentially reactive against self-components. These T cells essentially ignore the self-antigens because they are seen with low affinity, they occur at low abundance, or because they hide behind tissue or processing barriers.

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Figure 1: Two ways in which pathogens might trick the immune system into attacking its own cells.

References

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  1. the Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP) BP 163, Illkirch, 67404, CU de Strasbourg, France

    Christophe Benoist & Diane Mathis

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  1. Christophe Benoist
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  2. Diane Mathis
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Benoist, C., Mathis, D. The pathogen connection. Nature 394, 227–228 (1998). https://doi.org/10.1038/28282

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