Differential effects of cyclic adenosine 3′, 5′‐monophosphate on T cell cytotoxicity

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Abstract
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 area engaged in the effector‐target interaction. Functional studies utilizing different cAMP‐analog combinations further substantiate the involvement of the type II kinase.