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  • Title: Chronic TNF-alpha exposure impairs TCR-signaling via TNF-RII but not TNF-RI.
    Author: Aspalter RM, Wolf HM, Eibl MM.
    Journal: Cell Immunol; 2005 Sep; 237(1):55-67. PubMed ID: 16325164.
    Abstract:
    Chronic exposure to TNF-alpha has been shown to impair T cell-activation in mice and in humans. In the present study, we investigated a possible role of TNF-RII in this long-term effect of TNF-alpha. Chronic TNF-alpha exposure led to suppression of subsequent TCR stimulation (e.g., TCR/CD28-induced proliferation, cytokine production (IFN-gamma, TNF-alpha)) but left TCR independent restimulation unaffected. Activation of T cells during TNF-alpha exposure was required for the inhibitory effect on TCR stimulation. In contrast to the mouse model, the inhibitory effect of long-term TNF-alpha exposure was mediated via TNF-RII but not TNF-receptor I, and surface expression of the TCR/CD3 complex remained unchanged. Chronic TNF-RII triggering downregulated T cell activation at an early level, as TCR-induced calcium flux and IL-2 mRNA expression were impaired after preculture in the presence of anti-TNF-RII mAbs. Furthermore, chronic TNF-RII-stimulation specifically downregulated store operated calcium channels, which contribute to sustained TCR-induced calcium influx.
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