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Ribavirin modulates the conversion of human CD 4 + CD 25 − T cell to CD 4 + CD 25 + FOXP 3 + T cell via suppressing interleukin‐10‐producing regulatory T cell
Author(s) -
Kobayashi Tamaki,
Nakatsuka Katsuhisa,
Shimizu Masumi,
Tamura Hideto,
Shinya Eiji,
Atsukawa Masanori,
Harimoto Hirotomo,
Takahashi Hidemi,
Sakamoto Choitsu
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12005
Subject(s) - il 2 receptor , interleukin 7 receptor , foxp3 , t cell , biology , cytokine , immune system , microbiology and biotechnology , chemistry , immunology
Summary Because regulatory T ( Treg ) cells play an important role in modulating the immune system response against both endogenous and exogenous antigens, their control is critical to establish immunotherapy against autoimmune disorders, chronic viral infections and tumours. Ribavirin ( RBV ), an antiviral reagent used with interferon, is known to polarize the T helper ( Th ) 1/2 cell balance toward Th 1 cells. Although the immunoregulatory mechanisms of RBV are not fully understood, it has been expected that RBV would affect T reg cells to modulate the T h1/2 cell balance. To confirm this hypothesis, we investigated whether RBV modulates the inhibitory activity of human peripheral CD 4 + CD 25 + CD 127 − T cells in vitro . CD 4 + CD 25 + CD 127 − T cells pre‐incubated with RBV lose their ability to inhibit the proliferation of CD 4 + CD 25 − T cells. Expression of F orkhead box P 3 ( FOXP 3) in CD 4 + CD 25 − T cells was down‐modulated when they were incubated with CD 4 + CD 25 + CD 127 − T cells pre‐incubated with RBV without down‐modulating CD 45 RO on their surface. In addition, transwell assays and cytokine‐neutralizing assays revealed that this effect depended mainly on the inhibition of interleukin‐10 ( IL ‐10) produced from CD 4 + CD 25 + CD 127 − T cells. These results indicated that RBV might inhibit the conversion of CD 4 + CD 25 − FOXP 3 − naive T cells into CD 4 + CD 25 + FOXP 3 + adaptive T reg cells by down‐modulating the IL ‐10‐producing T reg 1 cells to prevent these effector T cells from entering anergy and to maintain Th 1 cell activity. Taken together, our findings suggest that RBV would be useful for both elimination of long‐term viral infections such as hepatitis C virus infection and for up‐regulation of tumour‐specific cellular immune responses to prevent carcinogenesis, especially hepatocellular carcinoma.