Selective Inhibition of Various Mitogen Responses in Human Lymphocytes

Abstract

Adenosine and deoxyadenosine are known inhibitors of the in vitro proliferative response of peripheral blood lymphocytes(PBL) to various mitogens(1–7). Erythro-9-(2-hydroxy-3-nonyl)-adenine hydrochloride (EHNA), an inhibitor of the enzyme adenosine deaminase(ADA), potentiates the inhibitory effects of both adenosine and deoxyadenosine. The incorporation of³H-leucirie into protein appeared to be a more sensitive index of adenosine toxicity than the incorporation of³H-thymidine(1). A differential sensitivity of cultured human T and B lymphoblasts towards the toxic effects of adenosine and deoxyadenosine has been observed: T cells are more sensitive than B cells(8,9). On the basis of³H-thymidine incorporation, mouse splenic cells stimulated by lipopolysaccharide(LPS) were less sensitive to the addition of adenosine than the concanavalin A(ConA) stimulated cells (10). Using a plaque forming cell assay, a biphasic effect of adenosine was seen on the in vitro antibody production in mice; concentrations of adenosine around 1mM stimulated antibody production in vitro, whereas concentrations above 1.5 mM had inhibitory effects (10).