Role of enhanced cellular adhesion in IL-6-augmented lymphokine-activated killer-cell function.
The authors demonstrated previously that a short-term treatment with IL-6 of lymphokine-activated killer (LAK) cells produces an increase in cytotoxic activity of CD56+/CD3- effector cells generated from human PBL as well as from human thymocytes. In the study described here, the mechanisms by which IL-6 enhances LAK cytotoxicity were examined. Like untreated LAK cells, IL-6-treated LAK cells require Ca++ to initiate cytolysis. However, IL-6 treatment of LAK cells does not alter the rate of programming for lysis. Instead, IL-6 increases target-binding capacity of CD56+/CD3- LAK cells in association with the increased cytotoxicity. Similar to target-binding of untreated LAK cells, the binding between IL-6-treated LAK cells and target cells is dependent on Mg++. Cellular adhesion molecules (CAM), CD11a-c, CD18, CD54, CD56, CD58 and CD2 (T11(1) epitope), are up-regulated in LAK cells by culture with IL-2. Among MoAbs to these CAMs, only Abs to CD11a/CD18 (LFA-1) and CD54 (ICAM-1) decrease both target-binding and cytolysis by LAK cells. IL-6 treatment changes neither the proportion nor the intensity of CAM positive cells. However, MoAbs to CD11a/CD18 and CD54 reduce both target-conjugation and cytotoxicity of IL-6-enhanced LAK cells to the same level as control LAK cells treated with the MoAbs. IL-6-enhanced LAK functions (both target-conjugation and target-lysis) are not abrogated by MoAbs to other CAM which do not inhibit standard LAK functions. These results indicate that IL-6 up-regulates cellular events mediated by CD11a/CD18 and CD54 molecules which are involved in standard LAK functions. These events may result in activation of lytic effector cells, associated with an increase in target-binding and an increase in cytotoxicity.
Iho
S
S
Division of Surgical Oncology, UCLA School of Medicine 90024.
Shau
H
H
D002448:Cell Adhesion; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D015850:Interleukin-6