High serum levels of soluble CD30 (sCD30) have been reported to better pred
ict the response to second line therapy in rheumatoid arthritis (RA). It is
believed that sCD30 is released by CD30(+) T cells present in the RA synov
ium, However, both the mechanism of recruitment to the joint and the functi
onal role of this T. cell subset in the pathogenesis of the disease remain
unknown. This study confirmed higher levels of sCD30 in the serum and synov
ial fluid (SF) of RA patients compared with normal controls. However, analy
sis of mRNA and cell surface CD30 expression showed that CD30(+) T cells ar
e detectable in the SF, but not in the synovial membrane. In contrast, T ce
lls expressing the CD30 transcript, but not the surface molecule, were foun
d in the peripheral blood of both RA and normal controls. CD30 surface expr
ession was up-regulated by adhesion and migration through endothelium in vi
tro and in a delayed-type hypersensitivity model in vivo. Although the grea
t majority of fresh or cloned CD30(+) T cells from SF produced both IFN-gam
ma and IL-4, CD30 expression strictly correlated with IL-4 synthesis in syn
ovial T cell clones. In addition, CD30(+) T cell clones also produced high
amounts of the anti-inflammatory cytokine IL-10. On this basis, we would li
ke to propose that synovial CD30(+) cells may play a role in the control of
the inflammatory response. Serum sCD30 may reflect such cell activity and,
therefore, explain the previously demonstrated correlation between high sC
D30 serum levels and positive response to therapy.