Analysis of accumulated T cell clonotypes in patients with systemic lupus erythematosus.

OBJECTIVE

To compare the accumulated T cell clonotypes in peripheral blood (PB) samples obtained at various times, and the accumulated T cell clonotypes in a PB sample and in an affected kidney, from patients with systemic lupus erythematosus (SLE).

METHODS

Peripheral blood mononuclear cells (PBMC) were obtained at 2-4 different times from each of 5 SLE patients, with or without flare-up of the disease; in addition, a biopsied kidney tissue sample was obtained from 1 of the patients. RNA was extracted from each sample and complementary DNA was prepared. Genes that encode the variable region of T cell receptor (TCR) B chains (BV) of 3 BV families, 5S1, 8, and 14, were amplified by reverse transcription-polymerase chain reaction (PCR), and the PCR products were cloned for sequencing.

RESULTS

A total of 877 cloned TCR genes was detected in the PBMC samples and the kidney sample. Oligoclonal T cell expansion was detected in 34 of the 36 PCR-amplified BV samples from PBMC (amplification of 3 BV families in 2-4 samples from 5 patients). The composition of clonally expanded T cell clonotypes was relatively stable in the patients with inactive SLE. In contrast, the composition of clonotypes in the PB changed drastically after the patient experienced the active phase of the disease. T cell clonotypes that had accumulated in the kidney appeared to be restricted and distinct from those that had accumulated in the PB of the same patient.

CONCLUSION

Different T cell clonotypes expand at different times and at different sites in patients with active SLE. The sensitizing antigens may change over the course of the disease and may be different at each site.