Multiple mechanisms of immunologic tolerance: novel approaches for unresponsiveness.

Abstract

I mmunologic tolerance is defined as a specific unresponsive state induced by prior exposure to an antigen or antigenic determinant. It is now clear that tolerance can be induced in both immature and mature lymphocytes of the T- or B-cell lineages. The mechanisms involved appear to be multiple: anergy (that is, the failure to respond to specific signaling), deletion of specific clones (via apoptosis), or suppression of reactivity, all of which may exist in the same organism depending on the antigen. Procedures to facilitate tolerance induction in adults who have made undesirable immune responses (for example, to blood products or red-cell antigens) will require novel approaches. We report here on data supporting a deletional mechanism by apoptosis in both neoplastic and normal murine B cells, and further describe protocols for the induction and maintenance of unresponsiveness in T- and B-lymphocyte clones in adult hosts.