Survival Factors from Activated Accessory Cells and their Role in Triggering Autoimmune Diseases

To maintain immune homeostasis, the immune system has evolved two “opposite” mechanisms to regulate the activation or expansion of effectors including potential auto-reactive lymphocytes following an immune response. One is to support the survival of activated effectors and thereby benefit the generation of memory response. However, an inappropriate survival of auto-reactive lymphocytes may lead to autoimmune diseases, e.g. multiple sclerosis (MS) and rheumatoid arthritis (RA). The other is to induce apoptosis of most activated effectors, thereby bringing the immune system to a baseline level after an immune response. It is known that autoimmune diseases are due to uncontrolled growth of auto-reactive lymphocytes, eventually leading to damage of self-tissues or organs. Control of auto-reactive T lymphocytes therefore constitutes an attractive therapeutic strategy. Many studies on accessory cells and their secreted factors have focused on their role in the effector phase of a specific autoimmune disease. Recent data, however, support their causative role in triggering autoimmune diseases. In the past several years, several cytokines from activated accessory cells were demonstrated to promote the survival of pathogenic auto-reactive lymphocytes in animal models of MS, RA, and other autoimmune diseases. This review therefore focuses on the current knowledge regarding the role of those soluble survival factors in the initiation of different autoimmune diseases.