Adenosine Inhibition of Lymphocyte-Mediated Cytolysis: Possible Role of Cyclic Adenosine Monophosphate

Abstract

The in vitro destruction of tumor cells by specifically sensitized mouse lymphocytes was inhibited by adenosine; this inhibition was markedly potentiated by the presence of an inhibitor of adenosine deaminase. The inhibition of cytolysis by adenosine was accompanied by a rapid elevation in lymphocytic adenosine 3',5'-monophosphate (cyclic AMP) concentrations. Both the inhibition of cytolysis and the elevation of cyclic AMP were reversed by prolonged incubation of the lymphocytes in the presence of adenosine or, more rapidly, by removal of the adenosine. Low concentrations of adenosine also caused an elevation of cyclic AMP in human lymphocytes, and this effect of adenosine may contribute to the lack of immune response associated with adenosine deaminase deficiency.

Purine Dysfunction in Cells from Patients with Adenosine Deaminase Deficiency

“…We have obtained preliminary data which suggests that lymphocytes are like red cells (17) and unlike fibroblasts in that they convert more adenosine to ATP than inosine at low adenosine concentrations. Previous lymphocyte toxicity data (I I) compared with the fibroblast data in Figures 6 and 8 suggest that lymphocytes may be slightly more sensitive to the toxic effects of adenosine than fibroblasts, although adenosine is an inhibitor of lymphocytemediated cytotoxicity (27) at adenosine levels (ID,, of .I5 mM) which are also toxic to fibroblast cell growth (shown in Figures 6 and 7). Fibroblast cell division and quantitative enzyme pathways may differ enough from that found in lymphocyte cells that few conclusions should be transferred from our work with fibroblasts to lymphocyte cell function.…”

Severe Combined Immunodeficiency in a Child with a Healthy Adenosine Deaminase Deficient Mother

“…The mother had less than 1% of normal ADA activity in both erythrocyte and lymphocyte extracts, but her whole peripheral blood lymphocytes demonstrated about 6% of normal activity. (7,8,10,18,19,21,24). Individuals with this form of SCID invariably have profound deficiencies of ADA activity in both erythrocytes and lymphocytes (1 2); however, there are reports of individuals with partial deficiencies of this enzyme who apparently have normal or near normal function of the immune system (3,11,13).…”

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

“…As CD39 is an ectoenzyme that degrades ATP to AMP, activated Treg cells are consequently not only able to abrogate ATP-driven maturation of dendritic cells [170], but also P2X7-mediated suppression of Treg function and stability in an autologous way [169]. The breakdown product of ATP was initially also reported as an inhibitor of lymphocyte mediated cytolysis which was associated with an elevation of cyclic AMP within the cytotoxic T cells [171,172]. Later on, others also revealed extracellular ATP to be a potent modulator in the cytolytic activity of cytotoxic T cells [173,174].…”