Table 2

Autoimmunity caused by single-gene defects. Mutations in regulatory molecules (either spontaneous or created by targeted gene disruption) lead to autoimmune diseases with distinct phenotypes in mice. AICD, activation-induced cell death.

Fas-FasLIL-2–IL-2Rα, βCTLA-4
Autoimmune disease
Multiple autoantibodies; nephritisHemolytic anemia; anti-DNA antibodies; inflammatory bowel disease (due to infection?)Tissue infiltration; autoantibodies?
Lymphoproliferation
Yes; accumulating cells are inert double-negative T cellsYes; accumulating cells are phenotypically normal, activated T and B cellsYes; accumulating cells are phenotypically normal, activated T and B cells
Postulated immunologic defects
Failure of AICD in CD4+helper T cells; failure to eliminate anergic B cellsFailure of AICD in CD4+ helper T cells; other defects in regulation?Failure of T cell anergy