How then could the observed pathological changes in the exocrine glands of patients with pSS be related to the various in vitro and in vivo laboratory findings? To begin with, the fact of inappropriate HLA-D/DR expression in epithelial cells in the absence of any infiltrating T cells or residual IFN-gamma must argue for an exogenous agent such as a virus that modulates the gene expression of epithelial cells. Such inappropriate expression is probably accompanied by the expression of other molecules that promote adhesion of lymphocytes in the proximal endothelium and infiltration into the exocrine gland. The autoimmune response takes place in these very exocrine glands and probably is initiated by the presentation of antigen(s) to the CD4+ T cells by the HLA-D/DR+ epithelial cells. The HLA-D/DR association shown in patients with pSS probably has to do with the antigenic fragments of the autoantigens that these molecules can preferentially bind to. The activated CD4+ T cells can then deliver help to specific B lymphocytes leading them to autoantibody-secreting plasma cells. In addition the extent of polyclonal activation of B lymphocytes and their potential for cytokine secretion and proliferation in vitro, is consistent with the view of virally-induced activation of these cells. The cross-reactivity to retroviral antigens observed in the sera of pSS patients, and the retroviral sequences detected in the salivary glands argue for some type of a retroviral infection of pSS patients in the course of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)