Types I and II interferons upregulate the costimulatory CD80 molecule in monocytes via interferon regulatory factor-1

B. Bauvois , J. Nguyen , R. Tang , C. Billard , J.-P. Kolb

CD80/B7.1 expressed on monocytes plays a prominent role in the activation of T-cell-mediated immunity and its level is reduced in monocytes from cancer patients. Type I (α/β) and type II (γ) IFNs are widely administered as adjuvant therapy. We show here that both classes of IFNs upregulate CD80 mRNA and protein in primary monocytes . The stimulatory action of IFN-α/β on CD80 is accompanied by the activation of both interferon regulatory factors IRF-1 and IRF-7, whereas IFN-γ stimulating effect is associated only with IRF-1 induction. IFNs concomitantly upregulate the transcription of CD40 costimulatory molecule whose activation is known to require IRF-1. In monocytic U937 cells, IRF-1 is activated by IFN-γ but not by IFN-α/β, whereas it is the reverse for IRF-7; in the latter cells, only IFN-γ is capable of stimulating CD80 transcription emphasizing the essential role of IRF-1. Moreover, siRNA against IRF-1 prevents IFN-γ-mediated CD80 activation. In AML cells, IFNs upregulate CD40, CD80 and IRF-1 in the FAB M4/M5 subtypes but not in the less differentiated M1/M2 subtypes. Monitoring the expression of CD80 on AML cells and its modulation by IFNs could help to predict the patients more susceptible to benefit from therapeutic strategies aimed at eliciting specific T cell responses to leukemia-associated antigens.

Mots clés: B7.1; antigen presenting cells; IRF-1; acute myeloid leukemia

B. Bauvois, J. Nguyen, R. Tang, C. Billard, J.-P. Kolb. Types I and II interferons upregulate the costimulatory CD80 molecule in monocytes via interferon regulatory factor-1. Biochemical Pharmacology, 2009, 78 (5), pp.514. ⟨10.1016/j.bcp.2009.05.005⟩. ⟨hal-00497271⟩