Deoxyadenosine modulates human suppressor T cell function and B cell differentiation stimulated by Staphylococcus aureus protein A.
Adenosine deaminase (ADA) deficiency and the resultant accumulation of deoxyadenosine (AdR) are associated with profound T cell dysfunction and variable B cell dysfunction in vivo. We examined the effects of AdR on the in vitro function of normal human peripheral blood B and T lymphocytes whose ADA activity was inhibited by 2'-deoxycoformycin. We found that OKT8+ T cell-mediated suppression of SPA-induced Ig production was markedly reduced by concentrations of AdR (3 to 10 microM) that did not affect helper T cell function. Because the lectin-induced proliferative responses of OKT8+ T cells and OKT8- T cells were equally susceptible to AdR, modulation of in vitro immune responses by low-dose AdR probably reflected different proliferative requirements for the expression of T cell helper or suppressor functions. Although low doses of AdR did not inhibit Ig production in SPA-stimulated cultures, we found that T cell-dependent, SPA-stimulated B cell proliferation was blocked by 3 to 10 microM AdR. Therefore, it appeared that B cell proliferation was not required for the induction of Ig synthesis in this system. Higher doses (30 to 100 microM) of AdR did block the induction of Ig synthesis, presumably by interfering with T-helper functions via a mechanism other than inhibition of proliferation and/or by inhibiting B cell differentiation events.
D000328:Adult; D000921:Antibody-Producing Cells / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D003839:Deoxyadenosines / Q000378:metabolism / Q000494:pharmacology*; D006462:Hemolytic Plaque Technique; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D013205:Staphylococcal Protein A / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000511:alpha-Macroglobulins / Q000502:physiology
D003839:Deoxyadenosines; D013205:Staphylococcal Protein A; D000511:alpha-Macroglobulins; C032306:polyclonal B cell activator