Expression of the retinoblastoma protein RbAp48 in exocrine glands

The Rockefeller University Press $30.00 J. Exp. Med. Vol. 205 No. 12 2915-2927 www.jem.org/cgi/doi/10.1084/jem.20080174 2915 Autoimmune disease is controlled by environments that include gene variants or various cytokines ( 1, 2 ). It can increase susceptibility to autoimmunity by aff ecting the overall reactivity and quality of the cells of the immune system. There is an autoimmune disease specifi c for certain organs in the body, involving a response to an antigen expressed only in those organs. Antigen/organ specifi city is aff ected by antigen presentation and recognition, antigen expression, and the state and response of the target organs ( 3, 4 ), which are maintained by a local immune system termed here “ local tolerance. ” Many mechanisms protect tissues from autoimmune damage. These include relative isolation from the immune system and inhibition of the function of invading lymphocytes. For example, the eye has barriers to T cell infi ltration and produces immunosuppressive cytokines, such as TGF( 5 ). Constitutive expression of Fas ligand within the privileged site might also prevent immune-mediated damage by eliminating Fas-expressing T cells ( 6 ). Although they have yet to be well demonstrated in spontaneous animal models or human disease, genetic eff ects at the level of tissue protection are therefore to be expected. Autoimmune organ damage can be mediated by CD4 + T cells, which play a crucial role in the development of autoimmunity ( 7 – 9 ). MHC class II alleles are probably involved in autoimmune disease because diff erent alleles have diff erent abilities to present peptides from target cells to autoreactive CD4 + T cells ( 10, 11 ). Certain class II alleles might predispose to autoimmunity by increasing positive selection or decreasing negative selection of autoreactive T cells in the thymus. They might also act by inhibiting selection in the thymus of the regulatory CD4 + T cells that are thought to prevent autoantigen-specifi c responses. Evidence for the local tolerance hypothesis is provided by the observation that CORRESPONDENCE Yashio Hayashi: [email protected]