APC activation by IFN-alpha decreases regulatory T cell and enhances Th cell functions.
Type I IFNs are central to a vast array of immunological functions. Their early induction in innate immune responses provides one of the most important priming mechanisms for the subsequent establishment of adaptive immunity. The outcome is either promotion or inhibition of these responses, but the conditions under which one or the other prevails remain to be defined. The main objective of the current study was to determine the involvement of IFN-alpha on murine CD4(+)CD25(-) Th cell activation, as well as to define the role played by this cytokine on CD4(+)CD25(+) regulatory T (Treg) cell proliferation and function. Although IFN-alpha promotes CD4(+)CD25(-) Th cells coincubated with APCs to produce large amounts of IL-2, the ability of these cells to respond to IL-2 proliferative effects is prevented. Moreover, in medium supplemented with IFN-alpha, IL-2-induced CD4(+)CD25(+) Treg cell proliferation is inhibited. Notably, IFN-alpha also leads to a decrease of the CD4(+)CD25(+) Treg cell suppressive activity. Altogether, these findings indicate that through a direct effect on APC activation and by affecting CD4(+)CD25(+) Treg cell-mediated suppression, IFN-alpha sustains and drives CD4(+)CD25(-) Th cell activation.
Pace
Luigia
L
Immunology Laboratory, Department of Biology, University of Rome Tor Vergata, Rome, Italy. Luigia.Pace@curie.fr
Vitale
Sara
S
Dettori
Beatrice
B
Palombi
Cecilia
C
La Sorsa
Valentina
V
Belardelli
Filippo
F
Proietti
Enrico
E
Doria
Gino
G
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015153:Blotting, Western; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D016898:Interferon-alpha / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053633:Receptor, Interferon alpha-beta / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C508032:Ifnar1 protein, mouse; C508034:Ifnar2 protein, mouse; D016898:Interferon-alpha; D007376:Interleukin-2; D053633:Receptor, Interferon alpha-beta