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

Abstract

A soluble membrane component of type III pneumococcal polysaccharide-coupled spleen cells (S3-SCSM) induces S3-specific suppressor T cells (Ts) in mice. These Ts can be detected only if mice are pretreated with cyclophosphamide (Cy) or if cells adherent to the lectin Vicia villosa are removed from the spleen cell population prior to transfer. The V. villosa-adherent spleen cells from mice injected with S3-SCSM could abrogate suppression mediated by Ts induced by S3-SCSM in Cy-treated mice. The V. villosa-adherent contrasuppressor cells were shown to be T cells that were I-J+ and of the Lyt-1 phenotype. Contrasuppressor T cells (Tcs) were not present in V. villosa-adherent spleen cell fractions obtained from normal mice, from mice injected with polyvinylpyrrolidone-coupled spleen cells, or from Cy-treated mice injected with S3-SCSM, i.e., mice in which Ts activity is dominant. The V. villosa-adherent cells that abrogated the activity of Ts induced by S3-SCSM in Cy-treated mice did not abrogate suppression mediated by a different subset of S3-specific Ts, suggesting that the Tcs described here do not have activity against all Ts subsets. The ability of S3-SCSM to activate Tcs in normal mice provides an explanation for the inability to detect S3-specific Ts in several previous studies.

Contrasuppression in autoimmunity. Abnormal contrasuppression facilitates expression of nephritogenic effector T cells and interstitial nephritis in kdkd mice.

“…Since the initial description of contrasuppression as an activity inhibitory of T cell suppression, and not attributable to excess helper activity (26), many studies (reviewed in 27) have verified the potent role ofcontrasuppression in influencing the expression of an immune response . Our observations regarding the counterbalancing effects of Ts and Tcs in this model ofspontaneous autoimmune disease are strikingly similar to those in models of induced immune responses to specific antigens (23,24,(28)(29)(30) . The relative insensitivity of anti-SRBC plaque-forming B 10 spleen cells to antigen-specific suppressor factors, for example, is dramati-cally altered by interfering with the contrasuppressor circuit in vitro (28) .…”

“…The effector Tcs cells in kdkd mice appear to be Lyt-2+, L3T4 -, T cells which bear I-J determinants and specifically bind to TBM antigens . Several investigators have described (22,24) effector Tcs as Lyt-1 +, 2-cells, in systems where the target cell of contrasuppression was an Lyt-l + cell . Phenotypic similarity between effector Tcs cells and their targets may reflect similar genetic restrictions .…”

“…Therefore, we next investigated the possibility that the suppressor mechanism was bypassed by an emergent contrasuppressor (Tcs) network. To pursue this hypothesis we used the observation from other antigenic systems that contrasuppressor cells adhere to the VV lectin (20,(22)(23)(24) . As shown in Table VII which could mediate a DTH response to CBA/Ca TBM.…”

Immunogenicity and immunochemistry ofStreptococcus pneumoniae capsular polysaccharides

“…Moreover, it induces IgG antibody formation and $3 immune memory in both high and low responder strains of mice. $3 coupled to syngeneic spleen cells can induce tolerance (Braley-Mullen 1982), regulated by antigenspecific Ts-and Tcs-cells, in euthymic but not athymic mice (Braley-Mullen 1984).…”