Dendritic Cells and Autoimmunity

Abstract

Autoimmune responses can arise because the repertoire of both T- and B-cell receptors, which allows recognition of pathogens, may contain receptors recognizing self-components. Ideally, autoreactive lymphocytes should be destroyed in the thymus during negative selection and induction of autoimmunity should be controlled. However, a great number of self-reactive lymphocytes escape thymic negative selection processes and form a peripheral pool of potentially autoimmune disease-mediating lymphocytes. On the other hand, self-tissues and -cells are routinely destroyed in our body and thus self-antigens are available in situ. If self-reactive lymphocytes are not completely destroyed in thymus by negative selection, autoantigens may activate these lymphocytes, and the feature of autoimmunity is developed. Thus, the autoimmune process is a normal phenomenon of living organisms. To block the activities of these autoreactive lymphocytes and minimize clinically apparent autoimmune diseases, another mechanism is active in situ. A population of tolerogenic immunocytes (T-regulatory cells) is present in our body. When these lymphocytes also fail to block progression of an autoimmune process, the pathological consequences of autoimmunity become manifest. It is therefore important to clarify the mechanisms leading to the initial activation of self-reactive lymphocytes that induce and sustain the autoimmune response. Also, insights are required regarding the causes underlying the inability of tissue-derived dendritic cells (DCs) to induce immune tolerance to self-antigens. In addition, another population of DCs, called regulatory DCs, should downregulate the autoimmune processes.