Introduction

Knowledge about T lymphocyte function has expanded dramatically in the 1990s, resulting in many advances in the understanding of the mechanisms underlying autoimmune diseases. T lymphocytes, initially believed to play a small role, if any, in autoimmune disease, are now implicated even in ‘antibody-mediated’ conditions such as pemphigus vulgaris. The undoubted advances in understanding autoimmune diseases have not, however, developed at the same pace for all conditions. More is known about T cell behaviour in multiple sclerosis and myasthenia gravis than in rheumatological conditions such as Sjögren's syndrome, SLE and RA. Indeed there are still claims, with some evidence, that T cells do not play a significant role at all in RA (Fox, 1997). In this chapter, we shall present some of the evidence implicating a pathological role for T cells in autoimmune rheumatic diseases particularly RA and discuss this in the context of recent advances in knowledge of T cell function. We will focus on the potential mechanisms triggering the activation of T cells, and on effector mechanisms. Finally, we will discuss potential strategies for the modulation of the autoimmune response in therapy.

Are T cells involved in autoimmune disease?

Genetic predisposition

Many population, family and twin studies have clearly demonstrated that genetic factors exert a major influence on predisposition to autoimmune disease. Reviewed in detail elsewhere (Theofilopoulos, 1995), the best-defined association is with genes from the class II region of the MHC. These highly polymorphic genes encode cell surface glycoproteins, which present peptides to CD4+T lymphocytes (Trowsdale, 1993).