T cell receptor repertoire of T cells in the kidneys of patients with lupus nephritis.
OBJECTIVE
To determine the role of T cells in the pathogenesis of lupus nephritis (LN).


METHODS
Renal biopsy specimens from 12 patients with systemic lupus erythematosus were used for the experiments. We analyzed T cell receptor (TCR) Vbeta1-20 family genes on intrarenal T cells and on peripheral blood lymphocytes (PBLs) by nested reverse transcriptase-polymerase chain reaction (PCR) and Southern blot analysis. Nucleotide sequence was determined in the third complementarity-determining region of the TCR Vbeta gene in expanded T cells. Messenger RNA (mRNA) expression levels of Th1 and Th2 cytokines on infiltrating T cells were measured by nested PCR.


RESULTS
The repertoire of TCR Vbeta in intrarenal T cells was relatively restricted compared with that in PBLs. The TCR Vbeta8 and TCR Vbeta20 genes were preferentially expressed in 6 of 12 patients (50%) and the TCR Vbeta9 and TCR Vbeta14 genes were expressed in 5 of 12 patients (42%). Junctional sequences of complementary DNA encoding the TCR Vbeta8 and TCR Vbeta20 genes in intrarenal T cells showed oligoclonal expansion, indicating antigen-driven stimulation. Interleukin-4 (IL-4) and IL-10 mRNA were highly expressed on intrarenal T cells, while interferon-gamma mRNA was not detected.


CONCLUSIONS
Our findings suggest that T cells infiltrating the kidneys of patients with LN may recognize restricted epitopes on antigens and function as Th2-type T cells.
Murata
Hideyuki
H
University of Tsukuba, Ibaraki, Japan. hdmurata@md.tsukuba.ac.jp
Matsumura
Ryutaro
R
Koyama
Akio
A
Sugiyama
Takao
T
Sueishi
Makoto
M
Shibuya
Kazuko
K
Tsutsumi
Akito
A
Sumida
Takayuki
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta