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.


CONCLUSIONS
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.
De Keyser
F
F
Department of Rheumatology, University Hospital Ghent, Belgium.
Elewaut
D
D
Overmeer-Graus
J P
JP
Van den Broek
P
P
Rijnders
A W
AW
Veys
E M
EM
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D017931:DNA Primers / Q000737:chemistry; D005434:Flow Cytometry; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000235:genetics*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D012218:Rheumatoid Nodule / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D017931:DNA Primers; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta