CD4 positive peripheral T cells from patients with systemic lupus erythematosus (SLE) are clonally expanded.
T cell activation was analysed in peripheral CD4+ T cells from both systemic lupus erythematosus (SLE) patients with active and inactive disease as well as in normal healthy donors (NHD) to investigate the involvement of CD4+ T cells in the etiopathogenesis of SLE. CD4+ T cell receptor (TCR) beta-chain transcripts, containing the complementarity determining region 3 (CDR3), were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analysed by high-resolution polyacrylamide gel electrophoresis. In addition the CDR3 of both clonally activated as well as heterogeneous Vbeta families from SLE patients were analysed at the molecular level. We observed a restricted CDR3 length polymorphism in peripheral CD4+ T cells from SLE patients compared with NHD, more pronounced in patients with high disease activity. Furthermore, in some Vbeta families single peaks in the histogram indicated nearly monoclonal T cell expansion. Sequencing of selected TCR beta-chains revealed a increased content of acidic amino acids in the CDR3 encoded by either proximal Jbeta elements or N nucleotides. We conclude that CD4+ T cells from peripheral blood of SLE patients display features of a secondary antigen driven immune response. The bias of the CDR3 towards acidic amino acids suggests the involvement of positively charged antigens.
Kolowos
W
W
Institute of Clinical Immunology, Department of Internal Medicine III, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
Gaipl
U S
US
Voll
R E
RE
Frank
C
C
Haas
J P
JP
Beyer
T D
TD
Kalden
J R
JR
Herrmann
M
M
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics* / Q000276:immunology; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D011110:Polymorphism, Genetic
D022801:Complementarity Determining Regions