Regulatory T Cell Deficiency in Systemic Autoimmune Disorders – Causal Relationship and Underlying Immunological Mechanisms

Abstract

Lupus disease is intriguing clinically and immunologically for its systemic nature and complexity in pathogenesis. Presence of autoantibodies to a diverse array of self antigens is a key feature of the disease. The broad B cell auto-reactivity is known to be predominately T cell-dependent, but the mechanism underlying such a systemic loss of self tolerance has yet to be fully understood. Regulatory T cells (Treg) play important roles in the maintenance of peripheral tolerance. These cells may exert their immunosuppressive effects on T effector cells (Teff) in an antigen-nonspecific way, possibly via their actions on the so-called antigen presenting cells (APC), dendritic cells (DC) in particular. Aberrant Treg frequencies and functions have recently been demonstrated both in lupus patients and in the animal models which develop spontaneously a lupus-like disease. These findings provided potentially therefore a plausible explanation for the systemic nature of the disease. However, there have been differences in the conclusions drawn from these various studies as to whether the lack of Treg-mediated control of auto-aggression is due to abnormal Treg frequency or functions. In this chapter, I’ll compare findings from these different studies and discuss their relevance in the context of systemic autoimmune disorders. The important issues here are about the causal relationship and underlying immunological mechanisms leading to the Treg abnormalities, as well as potential clinical implications in systemic autoimmunity