IL-2 induces Fas ligand/Fas (CD95L/CD95) cytotoxicity in CD8+ and CD4+ T lymphocyte clones. J Immunol 1997 Jun 15;158(12):5612-8
Date
06/15/1997Pubmed ID
9190908Scopus ID
2-s2.0-0031570374 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
IL-2 is a T cell growth factor that has pleiotropic functions in T cell differentiation, induction of lymphokine-activated killer cells, and regulation of immune responses. In studying TCR triggering of perforin or Fas ligand (FasL)/Fas (CD95 ligand/CD95) cytotoxicity in our influenza-specific T cell clones, we found that IL-2 can also induce FasL/Fas cytotoxicity. IL-2 induces FasL/Fas cytotoxicity in our CD8+ and CD4+ Th1 clones, but not in our CD4+ Th2 clones. IL-2 induction of cytolytic activity occurs when the CD8+ T cells are refractory to IL-2-induced proliferation. This killing is Ag independent, MHC unrestricted, and blocked by Fas.Fc fusion protein. IL-2 induces FasL/Fas cytotoxicity in a dose-dependent manner, but does not induce high levels of FasL expression as detected by flow cytometry. TCR triggered FasL/Fas cytotoxicity is detectable in CD8+ and Th1 clones by 3 h and peaks at 6 h; high levels of killing are maintained for at least 24 h. Similarly, IL-2 induces FasL/Fas killing in CD8+ and Th1 clones within 3 h of stimulation and maintains high levels for at least 24 h. TCR-triggered FasL/Fas killing is inhibited by emetine and cyclosporin A, whereas IL-2-induced FasL/Fas killing is inhibited by emetine, but not by cyclosporin A. These results demonstrate a second mechanism to induce FasL/Fas cytotoxicity in CD8+ and Th1 clones and may explain IL-2 induction of Ag-independent MHC-unrestricted lymphokine-activated killer cell activity.
Author List
Esser MT, Dinglasan RD, Krishnamurthy B, Gullo CA, Graham MB, Braciale VLAuthor
Mary Beth Graham MD Associate Chief, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antigens, SurfaceCD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Clone Cells
Cyclosporine
Cytotoxicity, Immunologic
Emetine
Fas Ligand Protein
Humans
Immunosuppressive Agents
Interleukin-2
Membrane Glycoproteins
Receptors, Antigen, T-Cell
T-Lymphocytes, Cytotoxic
Th1 Cells
Th2 Cells
fas Receptor
