Autoantigen-specific IL-10-transduced T cells suppress chronic arthritis by promoting the endogenous regulatory IL-10 response

T Guichelaar, CB ten Brink, PJ van Kooten… - The Journal of …, 2008 - journals.aai.org
T Guichelaar, CB ten Brink, PJ van Kooten, SE Berlo, CP Broeren, W van Eden, F Broere
The Journal of Immunology, 2008journals.aai.org
Deficient T cell regulation can be mechanistically associated with development of chronic
autoimmune diseases. Therefore, combining the regulatory properties of IL-10 and the
specificity of autoreactive CD4+ T cells through adoptive cellular gene transfer of IL-10 via
autoantigen-specific CD4+ T cells seems an attractive approach to correct such deficient T
cell regulation that avoids the risks of nonspecific immunosuppressive drugs. In this study,
we studied how cartilage proteoglycan-specific CD4+ T cells transduced with an active IL-10 …
Abstract
Deficient T cell regulation can be mechanistically associated with development of chronic autoimmune diseases. Therefore, combining the regulatory properties of IL-10 and the specificity of autoreactive CD4+ T cells through adoptive cellular gene transfer of IL-10 via autoantigen-specific CD4+ T cells seems an attractive approach to correct such deficient T cell regulation that avoids the risks of nonspecific immunosuppressive drugs. In this study, we studied how cartilage proteoglycan-specific CD4+ T cells transduced with an active IL-10 gene (T IL-10) may contribute to the amelioration of chronic and progressive proteoglycan-induced arthritis in BALB/c mice. TCR-transgenic proteoglycan-specific T IL-10 cells ameliorated arthritis, whereas T IL-10 cells with specificity for OVA had no effect, showing the impact of Ag-specific targeting of inflammation. Furthermore, proteoglycan-specific T IL-10 cells suppressed autoreactive proinflammatory T and B cells, as T IL-10 cells caused a reduced expression of IL-2, TNF-α, and IL-17 and a diminished proteoglycan-specific IgG2a Ab response. Moreover, proteoglycan-specific T IL-10 cells promoted IL-10 expression in recipients but did not ameliorate arthritis in IL-10-deficient mice, indicating that T IL-10 cells suppress inflammation by propagating the endogenous regulatory IL-10 response in treated recipients. This is the first demonstration that such targeted suppression of proinflammatory lymphocyte responses in chronic autoimmunity by IL-10-transduced T cells specific for a natural Ag can occur via the endogenous regulatory IL-10 response.
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