Anti-phenyltrimethylamino immunity in mice. II. L-Tyrosine-p-azophenyltrimethylammonium-induced suppressor T cells selectively inhibit the expression of B-cell clones bearing a cross-reactive idiotype.

Abstract

The anti-phenyltrimethylamino (TMA) response in A/J mice is characterized by a cross-reactive idiotype(s) (CRI) that appears linked to the Ig[immunoglobulin]-Ie allotype. These findings made it attractive to look for a CRI on T [thymus-derived] cells reactive to the same TMA determinant. A suppressor T cell (Ts) assay specific for L-tyrosine-p-azophenyl-trimethylammonium [tyr(TMA)] was developed. A/J mice were primed with tyr(TMA) in complete Freund''s adjuvant (CFA), L-tyrosine-azobenzenearsonate [tyr(ABA)] in CFA or with CFA alone. Six weeks later all mice were inoculated with TMA-bovine serum albumin (BSA) in CFA, boosted with soluble TMA-BSA 3 wk later and plaqued 7 days after the soluble boost. Priming with tyr(TMA) in CFA resulted in 66% suppression of anti-TMA plaque-forming cells (PFC) as compared with control groups primed with tyr(ABA) in CFA or CFA alone. The suppression was shown to be mediated by Ts, as only T cells but not B [bone marrow-derived] cells from suppressed animals transfer the suppression in adoptive cell transfer experiments into lethally irradiated recipients. The profile of the anti-TMA PFC in the suppressed and nonsuppressed animals was examined via incorporation of anti-idiotypic sera (specific for CRI-TMA) into the plaquing medium. Suppression of the major CRI+-TMA PFC was virtually complete, whereas the CRI--TMA PFC are left intact. When A/J mice were primed with idiotypic antisera (anti-Id) or normal rabbit serum (NRS) rather than with the antigen on CFA alone, and the same protocol was followed thereafter, anti-Id-inoculated mice were suppressed by 63% when compared with the NRS-primed controls. Again the suppression could be accounted for by exclusive elimination of CRI+ anti-TMA PFC. The possibility that the antigen-induced idiotype suppression may result from idiotypic restrictions between interacting CRI+-Ts and CRI+-B cells will be discussed.