Cutting edge: in vivo blockade of human IL-2 receptor induces expansion of CD56(bright) regulatory NK cells in patients with active uveitis.
In vivo blockade of the human IL-2R by mAb has been used for immunosuppression in transplantation, therapy for leukemia, and autoimmune diseases. In this study, we report that administration of a humanized IL-2R blocking Ab induced a 4- to 20-fold expansion of CD56(bright) regulatory NK cells in uveitis patients over time. The induced CD56(bright) regulatory NK cells from patients exhibited similar phenotype as those naturally occurring CD56(bright) cells. Patients with active uveitis had a significantly lower level of CD56(bright) NK cells compared with normal donors (p < 0.01). In addition, the induced CD56(bright) cells could secrete large amounts of IL-10 whereas CD56(dim) NK cells could not, suggesting that the induction of the CD56(bright) cells may have a beneficial effect on the remission of active uveitis. Our observation may have implications to IL-2R blockade therapy and for the potential role of CD56(bright) regulatory NK cells in autoimmune diseases.
Li
Zhuqing
Z
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Lim
Wee Kiak
WK
Mahesh
Sankaranarayana P
SP
Liu
Baoying
B
Nussenblatt
Robert B
RB
D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy; D019002:CD56 Antigen / Q000096:biosynthesis*; D000077561:Daclizumab; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors* / Q000276:immunology; D014605:Uveitis / Q000276:immunology* / Q000473:pathology / Q000628:therapy
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019002:CD56 Antigen; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2; D000077561:Daclizumab