Type 1 IFN maintains the survival of anergic CD4+ T cells. Academic Article uri icon


  • 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 cells 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-alphabeta 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-alphabeta 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 vivo.

published proceedings

  • J Immunol

altmetric score

  • 0.25

author list (cited authors)

  • Lombardi, G., Dunne, P. J., Scheel-Toellner, D., Sanyal, T., Pilling, D., Taams, L. S., ... Akbar, A. N.

citation count

  • 41

complete list of authors

  • Lombardi, G||Dunne, PJ||Scheel-Toellner, D||Sanyal, T||Pilling, D||Taams, LS||Life, P||Lord, JM||Salmon, M||Akbar, AN

publication date

  • October 2000