Objective. To study the presence of estrogen-binding sites (EBS) in the synovial tissues of male and female patients with rheumatoid arthritis (RA) and in age and sex-matched healthy controls.

Methods. Both type 1 (high affinity, low binding capacity) and type 2 (reduced affinity, higher binding capacity) EBS were investigated in both soluble and nuclear fractions of homogenized synovial tissue samples by a dextran-coated charcoal method. To determine what type of synovial cell was positive for EBS, cryosections of synovial tissues were immunostained with a specific monoclonal anti–estrogen receptor antibody (anti-ER MAb) using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with the anti-ER MAb and with specific MAb to detect different macrophage antigens (Ber-MAC3, MAC387, CD68) and CD8+ T cell subsets (CD29+, CD45RO+ and CD29–, CD45RO–) was performed.

Results. Higher affinity EBS were found mostly in nuclear cell fractions of either RA or control synovial tissues (28 of the 33). These EBS were present to a lesser extent in soluble cell fractions (11 of the 33). Immunostaining showed the estrogen receptor–positive cells to be the macrophage-like synoviocytes and the CD8+, CD29+ T cells both in RA and in control synovial tissues. Higher nuclear content of EBS was consistent with more intense nuclear staining of synoviocytes and T cells.

Conclusion. It is conceivable that the immunomodulatory activity exerted by estrogens is at least partly mediated through their interaction with EBS that are present on macrophage-like synoviocytes, functioning as antigen-processing and antigen-presenting cells, and on antigen-experienced (memory) CD8+ T lymphocytes (CD29+, CD45RO+).