Genetics of T Cell Defects in Lupus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies thatcause damage to multiple organs and tissues.Intrinsic defects have been demonstrated in the lymphoid andmyeloid cellular compartments,including T cells.Lupus susceptibility is mediated through the interplay of a largenumber of genes,most of which are still unidentified.Most of the genetic studies in both human patients and mousemodels have addressed lupus susceptibility as a whole.More recently however,more attention has been paid to theinheritance of specific lupus-associated phenotypes.In this review,we summarized our results obtained with theSlel locus in the NZM2410 mouse model,which mediates the generation of anti-histone autoreactive T cells.Slel,which is constituted of multiple genes,is the only known genomic region that is sufficient for the generation ofautoreactive T cells.The identification of the corresponding genes will constitute a landmark for our understandingof the mechanisms of autoimmunity.Our results are discussed in the context of candidate genes and the role of Tcells in systemic autoimmunity.Cellular & Molecular Immunology.2005;2(6):403-409.