Cellular interactions in immune regulation. Hapten-specific suppression by non-T cells and T cell-mediated reversal of suppression

Abstract

The ability of lymphoid cells from immunized animals to regulate the response of naive B ceils to the immunizing hapten was studied. Mice were immunized with trinitrophenylated (TNP) bovine gamma globulin (BGG) in complete Freund's adjuvant, and their spleen cells were examined in vivo and in vitro for the presence of specific inhibitory activity. This activity was found to peak 1 wk after immunization, was active against TNP on both T-dependent (BGG) and T-independent (Ficoll and polyacrylamide beads) carriers, and was demonstrable both by mixed cell transfers and mixed cell culture experiments. In in vitro studies, it was shown that the inhibition of the response to TNP- polyacrylamide beads by immune spleen cells was mediated by a non-T cell, possibly a B cell, because the suppressor activity was enriched in a purified B cell preparation. A role for macrophages was not formally ruled out. A specific suppressor factor was produced in vitro by immune spleen cells cultured in the absence of antigen. The suppressor activity was modulated by T .cells because elimination of T cells from the normal spleen cell population decreased suppression; elimination of T cells from the immune spleen cell population did not effect suppression, but elimination of T cells from both the normal and immune spleen cell populations allowed the expression of marked specific suppression. Thus, T cells present in the normal spleen cell population augment the degree of suppression, whereas T cells present in the immune spleen cell population decrease the degree of suppression; that is, T cells present in the immune spleen cell population had the ability to specifically abrogate suppression ("abrosuppression") in a T-independent immune response. It is proposed that the response to a T- independent antigen is regulated by specific suppressor activity generated by a non-T cell and augmented by the interaction of this cell with a T cell. The suppressor activity can be blocked by a specific abrosuppressor T cell. It is suggested that, because suppressor activity appears dominant in the naive state of the immune system, the induction of specific abrosuppressor activity may be essential if an immune response is to take place.

Regulation of the antibody response to type III pneumococcal polysaccharide by contrasuppressor T cells.

“…(2,5,22). It has previously (25) been suggested that the activation of T cells which can block Ts activity may be essential if an immune response is to take place. Tcs have also been shown (26) to be capable of interfering with tolerogenic signals in vivo and are important in allowing neonatal cells to exhibit positive immune function (16,21).…”

Hapten reactive inducer T cells. II. Evidence that a secreted form of the T cell receptor induces antibody production.

“…The double conjugates FITC-KLH-TNP or FITC-BGG-TNP were prepared by incubating 50 mg FITC (Sigma Chemical Co., St. Louis, MO) and 40 mg trinitrobenzenesulfonic acid (TNBS) (ICN Nutritional Biochemicals, Cleveland, OH) with 100 mg keyhole limpet hemocyanin (KLH) (Calbiochem-Behring Corp., San Diego, CA) or 100 mg bovine gamma globulin (BGG) in l0 ml of 2% K~COs at room temperature for 2 h, followed by rotation overnight at 4°C and extensive dialysis. Ficoli (mol wt 400,000 Pharmacia, Inc., Piscataway, NJ) and lipopolysaccharide (LPS) (Escherichia coli 0127:B8; Sigma Chemical Co.) were conjugated with E-TNP-L-lysine (ICN Nutritional Biochemicals) as described (8). TNP conjugated Brucella abortus (B.A.)…”

Hapten-specific responses to the phenyltrimethylamino hapten. III. Mice whose delayed-type hypersensitivity responses cannot be abrogated by the presence of anti-idiotypic suppressor T cells lack a critical modulatory T cell function.

“…The downregulation of the immune response by suppressor T cells (Ts) is complex and not fully understood. Recent reports describing the heretofore unrecognized immunoregulatory functions of T cells such as "contrasuppressors" (9) and "abrosuppressors" (10) add still more to the complexity involved in the biological function, immunoregulation.…”