Role for suppressor T cells in the pathogenesis of autoimmune diseases (including rheumatoid arthritis). Facts and hypotheses.
Although uncontrolled clones of autoreactive T cells play a central role in the pathogenesis of autoimmunity, another mechanism potentially involved in many autoimmune diseases is deficiency of suppressor T cells, most notably those belonging to the antiidiopeptide TH3/Tr1 TCD4+CD25+(high) subset. Failure of suppressor mechanisms may be in part primary, due to defective positive selection of suppressor T cells in the thymus, and in part acquired, secondary to chronic infections promoted by deficiencies in innate immunity. Renewed interest in suppressor TCD4+ cells has generated plausible explanations for many events including paradoxical induction of autoimmune disorders by immunosuppressive agents or thymectomy. Insights into the physiology of these regulatory T-cell clones might suggest new treatment options, although many currently used drugs (including anti-TNF alpha agents) enhance the activity of several suppressor T-cell clones. Investigation of these suppressor clones in rheumatoid arthritis is still in its infancy and faces obstacles such as the need for identifying key clones in each individual patient and the presence of T-cell repertoire contraction. This last phenomenon exists at disease onset and may stem from early thymus dysfunction, which may also lead to a reduction in suppressor TCD4+ cell counts. Thus, although restoring deficient suppressor clones may provide a full recovery in animals, the high prevalence of T-cell repertoire contraction in humans with rheumatoid arthritis may severely limit the beneficial effects of this therapeutic approach.
Berthelot
Jean-Marie
JM
Rheumatology Department, Nantes Teaching Hospital, 44093 Nantes cedex 01, France. jeanmarie.berthelot@chu-nantes.fr
Maugars
Yves
Y
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology*; D001327:Autoimmune Diseases / Q000209:etiology*; D006801:Humans; D008954:Models, Biological; D050378:T-Lymphocytes, Regulatory