Immunobiologic properties of the C8-derivatized guanine ribonucleosides

In recent studies from this laboratory, the immunologic properties of a new class of activator, the C8-derivatized guanine ribonucleosides have been described. These agents are potent lymphocyte activators which appear to gain access to the interior of the cell by the purine nucleoside facilitated transport mechanism and to activate the cell at an intracellular triggering site. Cyclic GMP does not appear to be a direct or indirect mediator of these events. The major lymphocyte population responsive to these compounds appears to be a mature group of B lymphocytes with a minor contribution provided by a subpopulation of less mature B cells. These nucleoside analogues exert a variety of pleiotropic effects, including polyclonal activation of B cells to secrete immunoglobulin, immunoenhancement of thymus-dependent and thymus-independent immune responses, induction of interleukin 1-like activity in cultured macrophages, and transmission of T cell-like inductive signals to B cells. This T cell-replacing activity appears to be T cell-independent and interleukin-2 independent, but is capable of synergizing with both T cells and T cell-derived lymphokines. Moreover, the T cell-like signals provided by the C8-derivatized nucleosides appear to be independent of the first signals (leading to clonal expansion) provided by these agents, in that antigen alone is able to provide a perfectly satisfactory inductive signal for B cells. Studies to date suggest that these nucleoside derivatives are capable of ameliorating immune deficits in serveral different models of murine immunodeficiency.