A cell-surface molecule selectively expressed on murine natural interferon-producing cells that blocks secretion of interferon-alpha

Blood 103:4201-4206, 2004

Speaker: 林士超                              Time: 11/24/2004, 15:10-16:00

Commentator: 蘇五洲 老師                     Place: Room 601

Abstract:

Interferon-producing cells (IPCs) are a small group of specialized leukocytes that secrete high levels of type I interferon inoculated with viruses or CpG motif.¹ For the reasons of rarity and complex phenotype (CD11c⁺, Ly-6C⁺, B220⁺, Gr-1⁺,and CD11b^-), it is quite difficult to distinguish IPCs from other immune cells. Within hybridoma cells they developed, the authors screened these cells and finding out one of them could secret a monoclonal antibody, mAb 440c, which exclusively recognized a surface molecule of murine IPCs (mIPCs). Using this mAb 440c, They successfully demonstrated the population of mIPCs in the blood and in all lymphoid organs under both normal and inflammatory conditions by flow cytometry and immunohistochemisrty; moreover, the mIPCs localize not only in T-cell zone of lymph nodes and the spleen but also in the liver. The distribution of mIPCs infiltrating into sentinel lymph nodes after inflammatory stimulation, they proved the hypothesis that the recruitment of IPCs into inflammatory sites.² Otherwise, the authors discovered the mAb 440c could inhibit the secretion of IFN-α without depleting mIPCs both in vivo and in vitro, and furthermore they also found that when mAb 440c conjugate with a neurotoxin, saporin would efficiently reduce the number of mIPCs. Altogether, the mAb 440c might be an useful tool for mIPCs identification and application in the excessive secretion of type I IFN diseases, such as autoimmune diseases.

References:

1. Siegal F. P., Kadowaki N., Shodell M. et al. The Nature of the Principal Type 1 Interferon-producing cells in Human Blood. Science 284, 1835-1837 (1999).

2. Cella M., Jarrossay D., Facchetti F. et al. Plasmacytoid monoctes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med. 5,919-923 (1999).

3. Blasius A., Vermi W., Krug A. et al. A cell-surface molecule expressed on murine natural interferon-producing cells that blocks secretion of interferon-alpha. Blood 103, 4201-4206 (2004).