Induction of specific transplantation immune reactions using anti-idiotypic antibodies.

Abstract

B and T lymphocytes with reactivity against major histocompatibility antigens are known to express this immune potential via a display on the outer surface of antigen-specific, idiotypic receptors. Here, we show that anti-idiotypic antibodies directed against such receptors may serve as specific triggering agents of the idiotype-positive lymphocytes in the physical absence of foreign histocompatibility antigens. This was shown in vitro using normal or immune spleen T cells where anti-idiotypic antibodies would lead to the selective proliferation and development of antigen-specific cytolytic T cells as determined by short-time 51Cr release assays. Furthermore, purified anti-idiotypic antibodies in adjuvant administered in vivo to normal syngeneic animals could be shown to lead to production of high titers of specific alloantibodies. The present experiments were in most cases carried out using auto-anti-idiotypic antibodies as triggering agents. The present results thus lend further support to the concept that idiotype-anti-idiotype reactions may be normal parts of conventional immune processes with either stimulatory or inhibitory consequences, depending upon the prevailing conditions.

T cell receptors with allo-major histocompatibility complex specificity from rat and mouse. Similarity of size, plasmin susceptibility, and localization of antigen-binding region.

“…This triggering of anti-T receptor antisera has been noted before (38,55) in situations where anti-idiotypic reagents with unusual power initiated specific T cells to mainifest immune functions of diverse natures. Availability of anti-T cell receptor sera of the present kind may allow a more refined analysis of the underlying requirements for this polyclonal triggering.…”

“…We have previously demonstrated that anti-idiotypic antisera directed against T cell idiotypes can stimulate T cells into proliferation and even generation of cytolytic T cells with relevant specificity (38). The antiserum 801 is a heteroantiserum that reacts with the majority of normal T lympocytes in mice and rats.…”

Sendai virus-specific T-cell clones: induction of cytolytic T cells by an anti-idiotypic antibody directed against a helper T-cell clone.

“…Auto-anti-idiotypic antibodies directed against allo-specific T-cell populations can stimulate a proliferative T-cell response as well as cytolytic T lymphocytes (12). Anti-idiotypic antibodies, directed against antigen-specific T-cell clones, have been shown to stimulate or inhibit T-cell functions in vitro (13,14).…”

“…Auto-anti-idiotypic antisera directed against T-cell populations stimulate a mixed leukocyte reaction (12). Several groups reported recently the generation of monoclonal antibodies by immunization of mice with cloned T-cell lines or hybridomas (13)(14)(15).…”

Suppression of tumor rejection by autologous anti-idiotypic immunity

“…Our (24), and that elimination of such anti-idiotypic lymphocyte clones by the use of anti-(anti)-idiotypic immunoreagents can increase the immune responses of certain clonotypes (25). Furthermore, anti-idiotypic reagents can, under defined conditions, stimulate the lymphocyte clones expressing the idiotype (6,26), even in the absence of antigen (27). Thus, anti-idiotypic and anti-(anti)-idiotypic immunoreagents may become very useful tools to specifically stimulate immune responses to tumor antigens.…”