DOMINANT T-CELL RECEPTOR REARRANGEMENTS IN INTERLEUKIN-2 EXPANDED LYMPHOCYTES FROM RHEUMATOID NODULES SUGGEST ANTIGEN-DRIVEN T-CELL ACTIVATION IN-SITU

Objective. To study at a molecular level the clonality of interleukin 2 (IL-2) expanded T cell lines derived from rheumatoid nodules. Such c ell lines were reported in earlier studies with flow cytometry and ant iidiotypic monoclonal antibodies (Mab) to be oligoclonal. Methods. T c ell lines were derived from rheumatoid nodules in 2 patients with rheu matoid arthritis (RA) and expanded in medium containing IL-2. Clonalit y was assessed by flow cytometry and T cell receptor (TCR) idiotype sp ecific Mab and by polymerase chain reaction with primers for V alpha a nd V beta gene families. Sequence analysis was performed in selected c ell lines. Results. In one patient, one cell line was identified with marked overexpression of V alpha 2 cells. Eleven V alpha 2 CDR3 sequen ces were derived from this cell line: 8 of these clones had an identic al CDR3 sequence and one other clone showed a related sequence. Five c ell lines derived from a second patient displayed a marked clonal bias to V beta 8 cells. One cell line with strong V beta 8 expression was chosen for further sequence analysis. Twelve V beta 8 sequences were o btained; 11 showed identical CDR3 sequences. Conclusion. Molecular ana lysis of TCR rearrangements in IL-2 expanded T cell lines from rheumat oid nodules strongly suggests that in situ T cell activation is relate d to classical antigen induced immune activation.