Cross-linking of 4-1BB up-regulates IL-13 expression in CD8(+) T lymphocytes.
4-1BB, one of co-stimulatory molecules, is a member of TNF receptor superfamily and expressed on T cells upon TCR ligation. We have shown that 4-1BB is a co-stimulatory molecule enhancing cell cycle progression and inhibiting activation-induced cell death of CD8+ T cells by enhancing TCR signaling pathways. Here, we first report that the cross-linking of 4-1BB increased the expression of IL-13 mRNA and protein, and its secretion apparently via calcineurin, a Ca2+/calmodulin-dependent phosphatase. Ligation of 4-1BB with p815-m-4-1BBL evoked intracellular Ca2+ level in CD8+ T cells. CD8+ T cells express IL-13 receptor alpha1 mRNA. Incubation with anti-IL-13 blocking mAb reduced proliferation of CD8+ T cells enhanced by 4-1BB, and the treatment of CD3/4-1BB-ligated CD8+ T cells with recombinant IL-13 enhances cell proliferation, indicating that 4-1BB-induced IL-13 expression is partially responsible for the CD8+ T cell expansion in an autocrine or paracrine manner.
The Immunomodulation Research Center and Graduate Program in Immunology and Biomedicine, University of Ulsan, Ulsan 680-749, South Korea.
Kyung-Ok
KO
Nam
Su-Mi
SM
Shin
Hyeon-Woo
HW
Lee
D053330:4-1BB Ligand / Q000378:metabolism*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015854:Up-Regulation
D053330:4-1BB Ligand; D003432:Cross-Linking Reagents; D018793:Interleukin-13; D002118:Calcium