Type 1 IFN maintains the survival of anergic CD4+ T cells

Anergic T cells have immunoregulatory activity and can survive for extended periods in vivo. It is unclear how anergic T cells escape from deletion, because both anergy and apoptosis can occur after TCR ligation, Stimulation of human CD4(+) T cell clones reactive to influenza hemagglutinin peptides can occur in the absence of APCs when MHC class II-expressing, activated T tells present peptide to each other. This T:T peptide presentation can induce CD95-mediated apoptosis, while the cells that do not die are anergic, We found that the death after peptide or anti-CD3 treatment of a panel of CD4(+) T cell clones is blocked by IFN-beta secreted by fibroblasts and also by IFN-alpha. This increases cell recovery after stimulation, which is not due to T cell proliferation, This mechanism for apoptosis inhibition rapidly stops protein kinase C-delta translocation from the cytoplasm to the nucleus, which is an early event in the death process. A central observation was that CD4(+) T cells that are rescued from apoptosis after T:T presentation of peptide by IFN-alpha beta remain profoundly anergic to rechallenge with Ag-pulsed APCs, However, anergized cells retain the ability to respond to IL-2, showing that they are nonresponsive but functional, The prevention of peptide-induced apoptosis in activated T cells by IFN-alpha beta is a novel mechanism that may enable the survival and maintenance of anergic T cell populations after TCR engagement. This has important implications for the persistence of anergic T cells with the potential for immunoregulatory function in vive.