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 cell lines were reported in earlier studies with flow cytometry and antiidiotypic monoclonal antibodies (MAb) to be obligoclonal.

METHODS: T cell lines were derived from rheumatoid nodules in 2 patients with rheumatoid arthritis (RA) and expanded in medium containing IL-2. Clonality was assessed by flow cytometry and T cell receptor (TCR) idiotype specific Mab and by polymerase chain reaction with primers for V alpha and V beta gene families. Sequence analysis was performed in selected cell lines.

RESULTS: In one patient, one cell line was identified with marked overexpression of V alpha 2 cells. Eleven V alpha 2 CDR3 sequences were derived from this cell line: 8 of these clones had an identical CDR3 sequence and one other clone showed a related sequence. Five cell 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 obtained; 11 showed identical CDR3 sequences.

CONCLUSION: Molecular analysis of TCR rearrangements in IL-2 expanded T cell lines from rheumatoid nodules strongly suggests that in situ T cell activation is related to classical antigen induced immune activation.