DNA microarray analysis of T cell-type lymphoproliferative disease of granular lymphocytes.
Lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the clonal proliferation of large granular lymphocytes of either T- or natural killer cell origin. To better understand the nature of T cell-type LDGL, we purified the CD4-CD8+ proliferative fractions from LDGL patients (n=4) and the surface marker-matched T cells isolated from healthy volunteers (n=4), and compared the expression profiles of 3456 genes using DNA microarray. Through this analysis, we identified a total of six genes whose expression was active in the LDGL T cells, but silent in the normal ones. Interestingly, expression of the gene for interleukin (IL) 1beta was specific to LDGL T cells, which was further confirmed by the examination of the serum level of IL-1beta protein. Given its important role in inflammatory reactions, the disease-specific expression of IL-1beta may have a causative relationship with the LDGL-associated rheumatoid arthritis. Spectratyping analysis of the T-cell receptor repertoire also proved the monoclonal or oligoclonal nature of LDGL cells. These data have shown that microarray analysis with a purified T-cell subset is an efficient approach to investigate the pathological condition of Tcell-type LDGL.
Second Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Hideki
H
Makishima
Fumihiro
F
Ishida
Toshiro
T
Ito
Kiyoshi
K
Kitano
Shuichi
S
Ueno
Ken
K
Ohmine
Yoshihiro
Y
Yamashita
Jun
J
Ota
Masao
M
Ota
Kazuyoshi
K
Yamauchi
Hiroyuki
H
Mano
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002455:Cell Division; D002460:Cell Line; D002999:Clone Cells; D004247:DNA / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D007694:Killer Cells, Natural / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000473:pathology
D007375:Interleukin-1; D012333:RNA, Messenger; D004247:DNA