Smith, Mark Duncan; (1996) An investigation into mycobacteria reactive T cells in rheumatoid arthritis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The relationship between mycobacteria and rheumatoid arthritis (RA) has been a matter of investigation for a number of years. The appearance of an arthritis in patients with tuberculosis was perhaps the first indication of a link between the 2 diseases. Arthritides have also been shown to arise as a result of infection, usually of the gastrointestinal or genito-urinary tract. A subset of T cells bearing the gamma delta (γδ) T cell receptor has also been implicated in the response against mycobacteria and this subset has been investigated in RA. The first question we set out to answer was whether the T cell responses to mycobacterial antigens differed between the peripheral blood and the synovial fluid of patients with RA. We have shown that the responses against certain mycobacterial antigens are elevated in T cells isolated from the synovial fluid of patients with RA when compared to T cells isolated from the peripheral blood of the same patient. The second question was whether T cells in RA are oligoclonal. This work, using monoclonal antibodies to the Vβ region of the T cell receptor, showed no selectivity in T cell receptor usage in RA. This study, however, did show oligoclonality in the T cells infiltrating the labial tissue of patients with primary Sjogren's Syndrome. Thirdly we have investigated the distribution of γδ T cells in patients with RA. Using monoclonal antibodies against the T cell receptor we showed a decrease in the percentage of γδ bearing cells in the peripheral blood of patients with RA and an increase in numbers in the synovial compartment. Furthermore, we showed an inversion of γδ T cell subsets in the synovial compartment. Finally, we have shown the expression of a receptor for the Fc region of immunoglobulin G (FcγRIII) on γδ T cells. The expression of this molecule is decreased on cells isolated from the synovial compartment of RA patients, and also on cells activated in vitro.

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