The role of interleukin-10 (IL-10) in IL-15-mediated T-cell responses.
Interleukin-15 (IL-15) is a potent T-cell stimulating factor, which has recently been used for pre-clinical in vivo immunotherapy. Here, the IL-15 effect on CD3-stimulated peripheral human T cells was investigated. IL-15 induced a significant T-cell proliferation and upregulated CD25 expression. IL-15 significantly enhanced T-cell production of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and IL-10. Between 10- and 100-fold greater concentrations of IL-15 were necessary to reach a biological effect equivalent to that of IL-2. Blockade of IL-2 binding to the high-affinity IL-2 receptor did not affect the IL-15 effects, suggesting that IL-15 did not act by inducing endogenous IL-2. Exogenously administered IL-10 significantly reduced the IL-15 and IL-2-mediated IFN-gamma and TNF-alpha production, whereas T-cell proliferation and CD25 expression were not affected. The inhibitory effects of exogenously administered IL-10 on T-cell cytokine production appeared indirect, and are likely secondary to decreased IL-12 production by accessory cells. Inhibition of endogenous IL-10 binding to the IL-10 receptor significantly increased IFN-gamma and TNF-alpha release from T cells. These data suggest that endogenous IL-10 can regulate activated T-cell production of IFN-gamma and TNF-alpha via a paracrine negative feedback loop. The observations of this study could be of relevance for the therapeutic use of IL-15 in vivo.
Körholz
D
D
Departments of Pediatric Hematology and Oncology and Dermatology, Laboratory of Immunology, Heinrich-Heine University Medical Center, Düsseldorf, Germany.
Banning
U
U
Bönig
H
H
Grewe
M
M
Schneider
M
M
Mauz-Körholz
C
C
Klein-Vehne
A
A
Krutmann
J
J
Burdach
S
S
D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology*; D019409:Interleukin-15 / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D019409:Interleukin-15; D011994:Recombinant Proteins; D016753:Interleukin-10