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Does the presence of self-reactive T cells indicate the breakdown of tolerance?
There are many experimental systems in which autoreactive T cells can easily be demonstrated but where the host does not normally develop autoimmune disease. How do these animals avoid autoimmunity? Does the presence of these self-reactive cells indicate the failure of self-tolerance? To answer these questions it is necessary to consider how some T cells might escape tolerance induction and why they are not activated in the host. There are several different explanations which can be broadly placed into one of two categories. First, although autoreactive cells may be easily stimulated under experimental conditions, the requirements for activation and likewise deletion may not be met under physiological conditions. The self-antigen may be poorly presented by APC or sequestered in a particular body compartment; alternatively, these T cells may have low affinity receptors needing high levels of antigen. The second category is characterized by the need for immunoregulation. A random selection of T cells may escape clonal inactivation in the thymus but may be kept under constant suppression, which provides a fail-safe mechanism for deletional tolerance. In this review we will discuss these mechanisms and their possible importance in the prevention of autoimmunity.
There are many experimental systems in which autoreactive T cells can easily be demonstrated but where the host does not normally develop autoimmune disease. How do these animals avoid autoimmunity? Does the presence of these self-reactive cells indicate the failure of self-tolerance? To answer these questions it is necessary to consider how some T cells might escape tolerance induction and why they are not activated in the host. There are several different explanations which can be broadly placed into one of two categories. First, although autoreactive cells may be easily stimulated under experimental conditions, the requirements for activation and likewise deletion may not be met under physiological conditions. The self-antigen may be poorly presented by APC or sequestered in a particular body compartment; alternatively, these T cells may have low affinity receptors needing high levels of antigen. The second category is characterized by the need for immunoregulation. A random selection of T cells may escape clonal inactivation in the thymus but may be kept under constant suppression, which provides a fail-safe mechanism for deletional tolerance. In this review we will discuss these mechanisms and their possible importance in the prevention of autoimmunity.