Idiotype suppression. III. Induction of unresponsiveness to sensitization with anti‐idiotypic antibody: identification of the cell types tolerized in high zone and in low zone, suppressor cellmediated, idiotype suppression

Abstract

Unresponsiveness of strain A/J mice to sensitization with guinea pig IgG anti‐A5A idiotypic antibody is induced by prior injection of guinea pig IgG2 anti‐A5A idiotypic antibody or unfractionated anti‐A5A antiserum. Two different forms of unresponsiveness could be induced depending on the dose of IgG2 anti‐A5A: high‐zone suppression was maximal one week after injection, could not be transferred by lymphocytes and disappeared within 3 to 4 weeks. Low‐zone suppression took 7 weeks to fully develop and could be transferred by splenic and lymph node T cells. High‐zone suppression is expressed as transient unresponsiveness in both the A5A‐idiotype‐positive T helper as well as B precursor cell compartments. Low‐zone, suppressor cell‐mediated suppression is expressed as chronic unresponsiveness in the A5A‐idiotype‐positive T helper cell compartment only, whereas the A5A‐idiotype‐positive B precursor cells remain fully responsive as revealed by addition of nonsuppressed T helper cells. These data satisfactorily explain that suppression of T helper cell‐independent idiotypes does not involve T suppressor cells. However, since the presence of suppressor T cells is accompanied by selective unresponsiveness of A5A‐positive B cells, the data imply that idiotypic restrictions exist for T‐B cooperation.

Quantitative studies on T cell diversity. I. Determination of the precursor frequencies for two types of streptococcus A-specific helper cells in nonimmune, polyclonally activated splenic T cells.

“…As antigens, we used either 3 × 105 SRBC/well or 1 x l0 T TNP-Strep A/well. Click's medium was used in these euhures in a 2% CO2 atmosphere, as previously described (25). After 4 d, responses were assessed by assay for direct plaque-forming cells (PFC) for TNP or SRBC, as previously described (25).…”

“…Click's medium was used in these euhures in a 2% CO2 atmosphere, as previously described (25). After 4 d, responses were assessed by assay for direct plaque-forming cells (PFC) for TNP or SRBC, as previously described (25). Positive PFC responses were determined by comparison with PFC responses of cultures that contained only B cells and antigen (Results).…”

“…At various times during the culture period, the cells were tested for helper function by using 1 × 105 cultured T cells together with 5 X 105 B cells and antigen as described above. Cells were also tested for suppressor function by adding 1 X 105 cultured T cells to 9 X l0 s spleen cells from mice previously primed with Strep A (25), cultured together with TNP-Strep A as described above. Responses of such euhures were assessed by assaying for direct PFC to TNP, as previously described (25).…”

“…it is difficult to prove that our helper cell frequencies indeed reflect a nonimmune state. In previous work we have shown that spleen cells of young mice in a clean colony produce marginal PFC responses to TNP-Strep A in vitro, whereas spleen cells of old mice and mice primed with Strep A produce high PFC responses (1,4,20,25) (K. Eichmann. Unpublished data.).…”

Network regulation among T cells; Conclusions from limiting dilution experiments

“…The first important principle that emerged was that injection of anti-idiotypic antibodies into the immune system in "physiological" quantities (1 injected antiidiotypic molecule per more than 106 circulating Ig molecules) can dramatically alter the function of the immune system [11,12,16,31,38,53]. Second, this alteration concerned both B and T cell functions, demonstrating that antibodies can recognize similar idiotypes on B and T cells [-2, 3, 9, 13, 16, 391.…”