Effects of deoxyadenosine on the activation of ADA inhibited T & B cells.

Using an in vitro model of adenosine deaminase deficiency, we have shown that the triggering of T lymphocyte proliferation by PHA is inhibited by concentrations of deoxyadenosine likely to occur in the plasma of ADA deficient children with severe combined immunodeficiency (ADA-SCID). Prostaglandin E1 increases the sensitivity of T cells to this inhibition, suggesting that derangement of cyclic nucleotide metabolism underlies the profound T lymphopaenia seen in ADA-SCID and in patients treated with the ADA inhibitor, deoxycoformycin. The proliferation and Ig synthesis of ADA inhibited B cells stimulated with protein A and EBV is in general less sensitive to the inhibitory effects of deoxyadenosine. However, this sensitivity varies widely between experiments suggesting that other cells present in the cultures may modify the inhibitory effect of deoxyadenosine. This may help explain the variability in B cell numbers and function in patients with ADA-SCID.