T-CELL-MEDIATED MAINTENANCE OF NATURAL SELF-TOLERANCE - ITS BREAKDOWNAS A POSSIBLE CAUSE OF VARIOUS AUTOIMMUNE-DISEASES

This paper shows that elimination of a small subpopulation of peripher al T cells can elicit activation/expansion of self-reactive T cells fr om the remaining T cells and produce a wide spectrum of organ-specific and systemic autoimmune diseases in normal mice; reconstitution of th e eliminated T-cell population prevents autoimmune development This re gulatory T-cell population expresses the CD25 molecule, apparently inc ludes 'activated' T cells, and suppresses immune responses to non-self as well as self antigens in an antigen-nonspecific manner. Although t he degree of abnormality in the T-cell regulation significantly influe nces the spectrum, incidence, and severity of autoimmune disease, the T-cell abnormality itself cannot determine the specificities of the el icited autoimmune responses since a comparable degree of abnormality c auses different autoimmune diseases depending on the mouse strains use d. Host genetic elements thus significantly contribute to determining the specificities. These findings taken together indicate that one asp ect of natural self-tolerance is maintained by a T cell-mediated or -d ependent control of potentially pathogenic self-reactive T cells in th e periphery, and that defective control, caused by environmental insul ts or genetic abnormalities, suffices to activate self-reactive T cell s, eliciting various autoimmune diseases depending on the genetic make up of the host. (C) 1996 Academic Press Limited