Ib. Mcinnes et al., INTERLEUKIN-15 MEDIATES T-CELL-DEPENDENT REGULATION OF TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION IN RHEUMATOID-ARTHRITIS, Nature medicine, 3(2), 1997, pp. 189-195
Citations number
40
Categorie Soggetti
Medicine, Research & Experimental",Biology,"Cell Biology
Tumor necrosis factor-alpha occupies a central role in rheumatoid arth
ritis (RA) pathogenesis. We now report that interleukin-15 (IL-15) can
induce TNF-alpha production in RA through activation of synovial T ce
lls. Peripheral blood (PB) T cells activated by IL-15 induced signific
ant TNF-alpha production by macrophages via a cell-contact-dependent m
echanism. Freshly isolated RA synovial T cells possessed similar capab
ility, and in vitro, IL-15 was necessary to maintain this activity. IL
-15 also induced direct TNF-alpha production by synovial T cells. In c
ontrast, IL-2 induced significantly lower TNF-alpha production in eith
er cell-contact-dependent or direct culture, and IL-8 and MIP-1 alpha
were ineffective. Antibodies against CD69, LFA-1 or ICAM-1 significant
ly inhibited the ability of T cells to activate macrophages by cell co
ntact.