Differential effects of cyclic adenosine 3',5'-monophosphate on T cell cytotoxicity.
We have investigated natural killer cell and T cell cytotoxicity using different assays and report a dual effect of cyclic adenosine 3',5'-monophosphate (cAMP) on T cell cytotoxicity depending on the activation status of the effector cell and the test system in question. cAMP enhanced the capacity of pre-activated T cells to induce DNA fragmentation in the target cell, while it inhibited spontaneous T cell cytotoxicity and natural killer cell cytotoxicity in conventional assays based on 51Cr release. The enhancement was most likely mediated by the cAMP-dependent protein kinase type II (cAKII), which is the particular isoform in T cells associated with the centrosome and the microtubule organizing center (MTOC). We show the complete co-localization of the cAKII with the centrosome after conjugate formation. Furthermore, the reorganization of the MTOC following conjugate formation brings the type II kinase into close proximity with the T lymphocyte membrane are engaged in the effector-target interaction. Functional studies utilizing different cAMP-analog combinations further substantiate the involvement of the type II kinase.
Ostenstad
B
B
Institute of Immunology and Rheumatology, Oslo, Norway.
Harboe
M
M
Lea
T
T
D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology*; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004249:DNA Damage; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000276:immunology; D008856:Microscopy, Fluorescence; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D000242:Cyclic AMP; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases