Interleukin-15 selectively expands CD57+ CD28- CD4+ T cells, which are increased in active rheumatoid arthritis.
Proinflammatory cytokines as well as CD4(+) T cells play critical roles in the pathogenesis of rheumatoid arthritis (RA). Recently, an increase of CD57(+) or CD28(-)CD4(+) T cells was demonstrated in RA, although the mechanism of the increase of these T cells is unclear. In this study, we first examined the relationship between CD57(+)CD4(+) T cells and CD28(-)CD4(+) T cells and found CD57(+)CD28(-)CD4(+) T cells, but neither CD57(+)CD28(+) nor CD57(-)CD28(+) cells, expanded in the peripheral blood of active RA. In vitro experiments revealed that CD57(+)CD28(-)CD4(+) T cells selectively expanded in response to IL-15. Furthermore IL-15-stimulated CD57(+)CD28(-)CD4(+) T cells induced TNF-alpha production from monocytes. These results suggest that CD57(+)CD28(-)CD4(+) T cells are involved in the pathogenesis of RA by responding to IL-15.
Yamada
Hisakata
H
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. hisakata@bioreg.kyushu-u.ac.jp
Kaibara
Nobutaka
N
Okano
Shinji
S
Maeda
Takeshi
T
Shuto
Toshihide
T
Nakashima
Yasuharu
Y
Okazaki
Ken
K
Iwamoto
Yukihide
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D018106:CD28 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D018959:CD57 Antigens / Q000096:biosynthesis*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018106:CD28 Antigens; D018959:CD57 Antigens; D019409:Interleukin-15; D014409:Tumor Necrosis Factor-alpha