Tissue antigens, sequestered behind anatomic barriers, do not contact T cells when the repertoire of "self' antigens are determined. Sequestered antigens are found in tissues such as the eye and testis. T cells are not rendered tolerant or anergic to the sequestered antigens. When antigens from these immunologically privileged sites contact immunocompetent cells, induction of an autoimmune disease results.
Sequestered antigens come into contact with the immune system following trauma to an organ. Autoimmune uveitis or sympathetic ophthalmia following an eye injury or orchitis following a vasectomy are examples of responses to sequestered antigens (Theofilopoulos, 1995). However, trauma alone does not always stimulate an immune response. Tissuetropic pathogens may be needed for the production of costimulatory molecules necessary for elicitation of the immune response.
Protection against autoimmune disease is facilitated by the expression of FasL. High levels of FasL are expressed on cells in immunologically privileged sites such as the eye and testis. These same cells lack the costimulatory B7 molecule. Activated T cells entering a target organ upregulate the expression of MHC II molecules via the secretion of IFN-y Endogenous antigens are presented to CD4 cells via the MHC II molecules. Without B7 costimulation, the Fas is upregulated and expressed on T cells. Linkage of Fas and FasL induces apoptosis in the autoreactive T cells (Dayan etal., 1997), preventing stimulation ofT cells.
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