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| INTERLEUKIN (IL)-15 IS A NOVEL CYTOKINE THAT ACTIVATES HUMAN NATURAL-KILLER-CELLS VIA COMPONENTS OF THE IL-2 RECEPTOR |
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| Author(s): CARSON WE, GIRI JG, LINDEMANN MJ, LINETT ML, AHDIEH M, PAXTON R, ANDERSON D, EISENMANN J, GRABSTEIN K, CALIGIURI MA |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 180 Issue: 4 Pages: 1395-1403 Published: OCT 1 1994 |
| Times Cited: 619 References: 25 |
| Abstract: Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and expressed. Whereas it has no sequence homology with IL-2, IL-15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct populations of highly purified human natural killer (NK) cells. The CD56(bright) subset of human NK cells constitutively expresses the high affinity IL-2R and exhibits a brisk proliferative response after the binding of picomolar amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep dose-response curve that was distinct from the dose-response curve for IL-2. The proliferative effects of IL-15 could be abrogated by anti-IL-2R beta (p75), but not by anti-IL-2R alpha (p55). The proliferative effects of IL-2 on CD56(bright) NK cells could be inhibited by both antibodies. CD56(dim) NK cells express the intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation of CD56(dim) NK cells by IL-15 was similar to that of IL-2 as measured by enhanced NK cytotoxic activity, antibody-dependent cellular cytotoxicity, and NK cell production of interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic activity could be completely blocked by anti-IL-2R beta monoclonal antibody. The binding of radiolabeled IL-2 and IL-15 to CD56(dim) NK cells was inhibited in the presence of anti-IL-2R beta. Scatchard analysis of radiolabeled IL-15 and IL-2 binding to NK-enriched human lymphocytes revealed the presence of high and intermediate affinity receptors for both ligands. IL-15 is a ligand that activates human NK cells through components of the IL-2R in a pattern that is similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by activated monocytes/macrophages. The discovery of IL-15 may increase our understanding of how monocytes/macrophages participate in the regulation of NK cell function. |
| Document Type: Article |
| Language: English |
Addresses:
1. ROSWELL PK CANC INST, DEPT MED, BUFFALO, NY 14263 USA
2. ROSWELL PK CANC INST, DEPT SURG, BUFFALO, NY 14263 USA
3. ROSWELL PK CANC INST, DEPT MOLEC MED, BUFFALO, NY 14263 USA
4. IMMUNEX RES & DEV CORP, SEATTLE, WA 98101 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: PJ703 |
| ISSN: 0022-1007 |
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