Abstract
Primary Sjögren's syndrome (SS) is characterised by focal lymphocytic infiltrates in salivary and lacrimal glands, leading to dryness of eyes and mouth, induction of class II major histocompatibility antigens on the glandular epithelial cells, and high titre antinuclear antibodies directed against ribonuclear proteins including Sjögren's-associated antigens (termed SS-A and SS-B). It is proposed that T-cells directed against self epitopes escape ‘tolerance’ in the thymus due to the relatively weak binding of a self peptide to self major histocompatibility complex molecules. As a result, these nascent T-cells with potential autoimmune reactivity are released into the peripheral lymphoid system. Subsequent exposure of these T-cells to the self peptide or a foreign (microbial) mimic in the salivary/lacrimal glands of SS patients can lead to expansion of these autoreactive T-cell clones and diversification of the T-cell response to include additional antigenic epitopes. Recent studies have emphasised the role of co-stimulatory factors including cytokines, growth factors, neurotransmitters, and reproductive hormones. Each of these sites of immune-neuro-hormonal interaction represents an opportunity for novel therapeutic intervention.