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IFN‐γ but not IL‐4 is important for mouse CD4+ T cell‐mediated macrophage activation following their exposure to pig cells in vitro
Author(s) -
Yi Shounan,
O'Connell Philip J.
Publication year - 2002
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1034/j.1399-3089.2002.01084.x
Subject(s) - cd40 , biology , t cell , microbiology and biotechnology , macrophage , cytokine , interleukin 12 , in vitro , immune system , immunology , cytotoxic t cell , biochemistry
In order to investigate the mechanism by which CD4+ T cells and macrophages interact in the xenogeneic immune response, murine CD4+ T cells and macrophages were used as responder cells in culture with irradiated fetal pig spleen cells (FPSC) as pig xenogeneic stimulators. In this in vitro model, murine CD4+ T cells and macrophages were cultured individually, or together with FPSC. In addition, mouse CD4+ T cells were also cultured with autologous macrophages which were previously stimulated by FPSC. The cultured murine cells were analyzed for expression of CD4+ T cell and macrophage activation markers (cell surface markers and cytokines) as well as cytokine production. CD4+ T cells and macrophages cultured alone or together without FPSC showed unchanged low levels of expression of activation markers. Coculture of macrophages with FPSC and in the absence of CD4+ T cells induced increased expression levels of all the activation markers examined except B7.2 and ICAM‐1. Addition of CD4+ T cells to the coculture further enhanced this up‐regulation. Coculture of CD4+ T cells with FPSC‐stimulated macrophages, but not naive macrophages, or FPSC alone, resulted in significantly increased numbers of CD4+ T cells coexpressing their activation markers, especially IFN‐γ and CD40L, and this expression was enhanced further by including FPSC in the coculture. The activation of both CD4+ T cells and macrophages in their coculture with FPSC was suppressed by neutralizing IFN‐γ but not IL‐4. Our results demonstrated that interaction of CD4+ T cells and autologous macrophages was required for their optimal activation in response to pig xenogeneic stimulation. The mechanisms involved included cell–cell and/or cytokine interactions, and in particular IFN‐γ mediated communication was involved. Macrophages activated by pig cells in the absence of CD4+ T cells were able to activate naive CD4+ T cells, thus providing an important communication pathway between innate immune activation and a T cell mediated response in xenograft rejection.