In vivo effects of anti-Ia alloantisera. I. Elimination of specific suppression by in vivo administration of antisera specific for I-J controlled determinants.

Abstract

The in vivo effects of i.v. administration of alloantisera directed to I-J subregion coded determinants were investigated. Anti-I-Jk [B10.A(3R) anti-B10.A(5R)] and anti-I-Js ([B10.A(3R) .times. B10.S(9R)]F1 anti-B10.HTT) antisera, when administered in 1-10 .mu.l amounts at the time of immunization, led to 2-fold increases in the Ig[immunoglobulin]M and IgG plaque-forming cells (PFC) responses to suboptimal doses of sheep erythrocytes in A/J (I-Jk) and SJL (I-Js) mice, respectively. To assess whether this immunopotentiation was due to a decrease in specific suppression, experiments were carried out using the polypeptide antigens random linear terpolymer of L-glutamic acid60, L-alanine30 and L-tyrosine10 (GAT) and random linear copolymer of L-glutamic acid50-L-tyrosine50 (GT), since administration of GAT to the nonresponder strain SJL, or GT to the nonresponder strain CBA, fails to induce a primary PFC response and stimulates specific suppressor T [thymus derived] cells able to prevent PFC responses to subsequent challenge with the immunogens GAT-methylated bovine serum albumin (MBSA) or GT-MBSA, respectively. CBA (I-Jk) mice given 100 .mu.g GT in Maalox-pertussis adjuvant on day 0 and 10 .mu.l anti-I-Jk antiserum i.v. on days 0, 1 and 2, develop a significant primary specific PFC response on day 7. A similar responsiveness to 10 .mu.g GAT is foundin SJL mice treated with 10 .mu.l anti-I-Js antiserum for 3 days. This same active anti-I-Js antiserum does not permit CBA mice to respond to GT, demonstrating the specificity of the anti-I-J effect. Anti-I-J antiserum treatment at the time of antigen administration reduced suppressor responses to GAT or GT, permitting primary PFC responses. To directly demonstrate such an effect on suppressor activity, SJL or CBA mice treated, respectively, with GAT or GT to induce suppressor cells active on GAT-MBSA or GT-MBSA responses after adoptive transfer to normal syngeneic recipients were also given anti-I-J antisera (10 .mu.l/day) for 3 days, at which time their spleen cells were tested for suppressive activity upon transfer. Cells from such treated mice failed to show detectable suppressive activity upon transfer to syngeneic recipients challenged with GAT-MBSA or GT-MBSA, confirming the hypothesis of an in vivo effect of anti-I-J antiserum on suppressor activity.