Relative sensitivity of human T cell subsets to deoxyadenosine toxicity

In the presence of adenosine deaminase (ADA) inhibitors, human T cells are highly sensitive to the cytotoxic action of deoxyadenosine (dAdo). On this basis, patients with T cell malignancies have been treated with the ADA inhibitor, deoxycoformycin. It is not known, however, whether T suppressor/cytotoxic (Leu 2a+) and T helper/inducer (Leu 3a+) subsets have different sensitivities to dAdo toxicity. In the present study, peripheral blood T (E+) cells from normal volunteers were incubated with dAdo in the presence of the ADA inhibitor, EHNA, and the proportion of viable Leu 2a+ and Leu 3a+ cells compared after 1, 2 and 3 days. Leu 2a+ T cells were found to be significantly more sensitive than Leu 3a+ cells as evidenced by an increase in the Leu 3a+/Leu 2a+ ratio from 1.9 to 3.0 over 3 days. This finding was confirmed by comparing the cytotoxic action of dAdo on separated Leu 2a+ and Leu 3a+ T cells. The action of dAdo on T helper and T suppressor cell function in antibody responses by human blood lymphocytes was also tested. As Leu 2a+ T cells were more sensitive to the cytotoxic action of dAdo than Leu 3a+ T cells, it was thought that a dose of dAdo plus EHNA could be chosen which would abrogate suppression but leave T helper cell function intact. We were, however, unable to obtain this result indicating that the biochemical mechanism by which T helper and suppressor cells are functionally inhibited is different to that resulting in cell death, and is unable to discriminate between them.