Arenas Where Downregulation May Operate

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Where can we hope to learn more about secondary mechanisms that might provide a window for infection-dependent autoimmunity? Table 4 lists conditions where these might be expected to operate, and indeed in several cases have been found to do so.

Finally, it is well established that one way or another infection influences susceptibility to autoimmune disease. Two comprehensive reviews discuss

Table 4 Systems known or likely to involve downregulation

Autoimmunity driven by monoclonal T or B cells

Long-term transplant survival, particularly when incompatible only at minor antigens Models of fluctuating autoimmunity

Immunological genes associated with autoimmune disease

Collagen induced arthritis [65]

Experimental allergic encephalomyelitis [39, 83]

Optic neuritis [8]

Neuritis [90,116]

Diabetes [33, 43]

Gastritis [1, 18]

Lupus [59]

Epithelial [80]

Cardiac, mouse [106] human [77] Renal, human [56, 96]

EAE in SJL mice [45] Arthritis post-cell transfer [57] Arthritis induced by type IX cartilage [75] T1D [29]

the range of mechanisms that may underlie this association [7, 97]. To this discussion, we would add only that attractive as the hygiene hypothesis is to explain the association, it should not be accepted uncritically [117].

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