Types I and II interferons upregulate the costimulatory CD80 molecule in monocytes via interferon regulatory factor-1.
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 (alpha/beta) and type II (gamma) IFNs are widely administered as adjuvant therapy. We show here that both classes of IFNs upregulate CD80 mRNA and protein in primary monocytes ex vivo. The stimulatory action of IFN-alpha/beta on CD80 is accompanied by the activation of both interferon regulatory factors IRF-1 and IRF-7, whereas IFN-gamma 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-gamma but not by IFN-alpha/beta, whereas it is the reverse for IRF-7; in the latter cells, only IFN-gamma is capable of stimulating CD80 transcription emphasizing the essential role of IRF-1. Moreover, siRNA against IRF-1 prevents IFN-gamma-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.
Bauvois
B
B
INSERM, U872, Paris F-75006, France. brigitte.bauvois@crc.jussieu.fr
Nguyen
J
J
Tang
R
R
Billard
C
C
Kolb
J-P
JP
D018122:B7-1 Antigen / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D050856:Interferon Regulatory Factor-1 / Q000502:physiology*; D007370:Interferon Type I / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology*
D018122:B7-1 Antigen; D017931:DNA Primers; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I; D007371:Interferon-gamma