Role of CD30 ligand (CD30L) positive T cells in the modulation of the inflammatory response in rheumatoid synovitis

CD30 and CD30 ligand (CD30L) are members of TNF-Receptor and TNF superfamilies, respectively. T cells ex- pressing CD30 are increased in several human diseases and in- teraction of CD30L with CD30+ cells induces signals that cause cell proliferation or apoptosis. A percentage of lymphomonocytes from synovial fluid (SF) from patients affected by Rheumatoid Arthritis (RA) express surface CD30 and high levels of soluble CD30 (sCD30) have been shown both in sera and SF of RA pa- tients. The increase of sCD30 levels seems to reflect the recruit- ment of CD30+ T cells into the inflamed joints and is predictive of a positive response to immunosuppressive therapy. Recently a soluble form of CD30L has been described in RA patients’ sera. Our aim was to investigate the role of sCD30L in RA. Materials and Methods. We have used cells from peripheral blood and SF and sera from RA patients. RA patients were treat- ed either with DMARDs or TNFα blockade therapy. We have analysed the cell surface expression of CD30L in T lymphocytes from peripheral blood (PB) and SF of patients with RA and in Jurkat cell line by flow-cytometry. Samples were also tested for membrane expression of CD30, CD127 and for intracellular FOX-P3. CD30L surface expression was validated by RT-PCR of the CD30L gene and by Western Blot and by Immunoprecip- itation of the molecule from RA T lymphocytes. Soluble CD30L was detected by ELISA assay in sera and SF of RA patients. Results. In PB and SF of RA patients a percentage of lympho- cytes expressed surface CD30L and CD30; CD30L and CD30 are not expressed on the same cells. CD30L+ T lymphocytes from SF did not show a Treg phenotype, while a percentage of CD30+ T lymphocytes was FOXP3+. Interestingly nearly 50% of CD4+/FOXP3+/CD127- cells are CD30+ cells. RT-PCR of the CD30L gene, Western Blot and Immunoprecipitation of CD30L from cells surface validated the presence of this molecule in lymphocytes of RA patients. sCD30L was not detectable in PB of healthy controls whereas it was present in PB and SF of patients with RA showing a correlation with the disease activity particularly in patients treated with TNFα blockade therapy. Conclusions. The expression of CD30L on the surface of a percentage of T lymphocytes from SF of patients affected by RA may reflect the Th1 pro-inflammatory response in this set- ting. The high levels of sCD30L both in sera and SF suggest that CD30L can be shedded as a functional active molecule as CD30 is. In this way sCD30L may induce apoptosis of CD30+ T cells leading to increased inflammation. Therefore, the cor- relation between the levels of this molecule and the response to TNFα-blockade therapy makes CD30L an interesting pre- dictor of response to the therapy itself.