Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) II. Cellular source and effect on responder and nonresponder mice.

Abstract

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder strains of mice, but does stimulate the development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT antibody responses to GAT complexed to methylated bovine serum albumin (GAT-MBSA). Furthermore, extracts prepared from lymphoid cells of GAT-primed, but not control, nonresponder mice inhibit the development of antibody responses to GAT-MBSA by normal nonresponder mice. This suppression is specific, dose-dependent, and can be readily analyzed in vitro. The suppressive factor is a T-cell product. An extract from GAT-primed DBA/1 mice inhibits the response to GAT-MBSA by spleen cells from histoincompatible strains of mice that are nonresponders to GAT, but not strains that are responders to GAT.

Immunosuppressive factors from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10. IV. Lack of strain restrictions among allogeneic, nonresponder donors and recipients.

“…Clearly, GAT-TsF can be produced by GAT-primed mice bearing any one of the three nonrespender haplotypes. Repeated titrations of a given extract have been remarkably consistent although some variation in suppressive activity from one batch to another has been observed (3).…”

“…GATTsF was also bound by GAT-Sepharose (group C) and was eluted from GATSepharose with 3.0 M KC1 (group D). The apparent increase in activity ofeluted GAT-TsF is frequently observed and is most likely due to removal of nonspecific enhancing material present in crude extracts (3). Purified GAT-TsF, eluted from GAT-Sepharose, is no longer absorbed by rabbit anti-GAT-Sepharose (group E).…”

“…Cell-free extracts of lymphoid cells from GAT-primed mice were prepared as previously described (3). Briefly, mice were injected i.p.…”

“…GAT-TsF has been detected in extracts from two nonresponder strains of mice (DBA/1 and A.SW) (3). In addition, an extract from GAT-primed DBA/1 mice inhibits the response to GAT-MBSA by spleen cells from a histoincompatible nonresponder strain of mice (A.SW) but not a histoincompatible responder strain (C57BL/6) (5).…”

Feedback suppression of the immune response in vitro. I. Activity of antigen-stimulated B cells.

“…Thus, it is not surprising that the immune system has evolved a sophisticated regulatory apparatus for preventing excessive responses to antigenic stimulation. The specific mechanisms so far described include (a) classical antibody feedback which is believed to operate by interference with cellular recognition of antigenic determinants (1, 2) and (b) development of suppressor T lymphocytes (Ts) 1 (3,4), recognizing either antigenic (5) or idiotypic (6) determinants and functioning in part by the release of subcellular effector molecules (7)(8)(9)(10). Until now, these two broad categories have been considered as largely independent pathways.…”