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CD4 positive peripheral T cells from patients with systemic lupus erythematosus (SLE) are clonally expanded

U S Gaipl

R E Voll

Institute of Clinical Immunology, Department of Internal Medicine III, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany

C Frank

J P Haas

Department of Pediatrics, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany

T D Beyer

J R Kalden

Institute of Clinical Immunology, Department of Internal Medicine III, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany

M Herrmann

Institute of Clinical Immunology, Department of Internal Medicine III, Friedrich-Alexander-University Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.

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) b-chain transcripts, containing the complementarity determining region 3 (CDR3), were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analysed by highresolution polyacrylamide gel electrophoresis. In addition the CDR3 of both clonally activated as well as heterogeneous Vb 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 Vb families single peaks in the histogram indicated nearly monoclonal T cell expansion. Sequencing of selected TCR b-chains revealed a increased content of acidic amino acids in the CDR3 encoded by either proximal Jb 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.

Key Words: SLE • CD4/ T cell expansion • acidic CDR3 • spectratyping

Lupus, Vol. 10, No. 5, 321-331 (2001)
DOI: 10.1191/096120301671176280


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