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Modulation of adhesion molecules on human large granular lymphocytes by interleukin-2 in vivo and in vitro
P L Triozzi1, D M Eicher, J J Rinehart
1Department of Medicine, The Ohio State University, Columbus.
Insights
Interleukin-2 (IL-2) therapy increases intercellular adhesion molecule-1 (ICAM-1) on large granular lymphocytes (LGL) in cancer patients. This immune modulation enhances LGL effector functions during immunotherapy.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Large granular lymphocytes (LGL) are crucial immune effectors.
- Interleukin-2 (IL-2) is a cytokine used in cancer immunotherapy.
- Adhesion molecules regulate lymphocyte interactions and function.
Purpose of the Study:
- To investigate the effect of IL-2 on adhesion molecule expression in human LGL.
- To determine if IL-2 influences intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) on LGL.
- To compare IL-2's effects with other cytokines like IL-1, IFN-gamma, and TNF.
Main Methods:
- In vivo and in vitro studies using human LGL from cancer patients.
- Isolation and purification of LGL via Percoll gradient centrifugation.
- Flow cytometry analysis using monoclonal antibodies (Leu 19/CD56) to identify LGL.
- Treatment of LGL with IL-2, IL-1, IFN-gamma, and TNF.
Main Results:
- IL-2 significantly increased ICAM-1 (CD54) expression on LGL, both in vivo and in vitro.
- IL-2 maintained the expression of LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), and p150,95 (CD11c/CD18) on LGL.
- IL-1, IFN-gamma, and TNF did not induce ICAM-1 expression on LGL.
- IL-2's effects on ICAM-1 and CD18 complex were also observed on other lymphocyte populations.
Conclusions:
- IL-2 enhances ICAM-1 expression on human LGL and other lymphocytes.
- IL-2 plays a key role in maintaining the expression of the CD18 adhesion molecule complex on LGL.
- These findings suggest IL-2-mediated adhesion molecule modulation is important for LGL effector functions in immunotherapy.
Abstract:
The modulation of adhesion molecules on human large granular lymphocytes (LGL) by interleukin (IL)-2 was investigated both in vivo and in vitro. Intercellular adhesion molecule-1 (ICAM-1; CD54) expression increased on LGL of cancer patients receiving IL-2 adoptive immunotherapy. ICAM-1 expression on LGL isolated by Percoll gradient centrifugation, LGL purified, and expanded by adherence to plastic surfaces and LGL identified by Leu 19 (CD56) monoclonal antibody were increased significantly in response to IL-2 in vitro. Exposure of LGL to IL-1, interferon (IFN)-gamma, and tumor necrosis factor (TNF) in vitro did not induce ICAM-1. The expression of LFA-1 (CD11a/CD18), a receptor for ICAM-1, and other leukocyte adhesion molecules, including Mac-1 (CD11b/CD18) and p150,95 (CD11c/CD18), was only maintained by IL-2. IL-2 induction of ICAM-1 and the maintenance of CD18 complex expression on small lymphocytes separated by Percoll gradients were similar to that on LGL. We conclude that IL-2 enhances the expression of ICAM-1 on multiple human lymphocyte populations including LGL effectors. Expression of the CD18 complex on LGL does not appear to be highly regulated by IL-2. These findings may have implications relevant to the role of these adhesion molecules in the activities of LGL modulated by IL-2.