Role of T cells in autoimmune disease

The thymus plays a vital role in the development of self-tolerance and thus abnormalities affecting the development or functioning of the thymus may contribute to the development of autoimmune diseases. For example, a variety of thymic abnormalities have been reported in systemic lupus erythematosus but it is unclear whether these are causative, or sequelae of the disease.

The TCR repertoire in autoimmune diseases: Evidence suggests that autoimmune disease is associated with restricted usage of particular TCR V region genes. In rheumatoid arthritis, studies have indicated that restriction of the TCR gene repertoire is limited to the genes of the junctional region of the TCR on CD8+ cells.

Table 5.8 Mechanisms involved in the breakdown of Tcell tolerance

Cause of abnormal self-antigen Effect production

Abnormal synthesis or Self-antigen with novel antigenic determinants processing of self-antigen

Drugs e.g. Aspirin may combine with proteins in the tissues resulting in a new antigenic complex

Viruses or drugs Novel association of different proteins (either self or viral) resulting in new antigenic determinants

Antigenic mimicry Non-self, cross-reactive antigens stimulateTcells which may then recognise self-antigens

In myasthenia gravis, patients have increased expression of the Vb5.1 (variable region gene 5.1 on the beta chain) and Vb8 genes in the peripheral blood and on mature thymocytes but not on precursor thymic cells. This suggests that these patients may exhibit an altered thymic selection process.

T helper cells: Self-tolerance is maintained even though autoreactive B cells may be present. This is thought to be because T cell tolerance is long-lasting and therefore autoreactive B cells lack the T cell help they require. This T cell control may be demonstrated in vitro by the use of B cell mitogens or purified lymphokines, which eliminate the need for T cell help. In vivo, T cell maintenance of tolerance may be overcome in a number of ways (Table 5.8).

T regulatory cells: A subpopulation of T cells has been identified that plays a role in preventing organ-specific autoimmune diseases. These T regulatory cells (Treg) tend to be in functional excess such that they prevent the development of T cell-mediated autoimmunity. It has been suggested that autoreactive T cells secrete IL-2 leading to an expansion of Treg cells, which could then switch off the autoreactive cells.

A further group of regulatory T cells (natural killer T cells - NKT) are a minor subpopulation which play a key role in regulating the immune response through the rapid production of IL-4 and IFNg. These cells have been shown to be deficient in persons with autoimmune, Type I diabetes. They are able to recognise lipid antigens in association with CD1 and respond by proliferation and the release of IL-4, IFNg and IL-10, promoting a Th2-type response and abrogating the autoreactive T cell response.

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