Presence Of Suppressor Research Articles

Precise Chemistry Control Using Cyclic Stripping Voltammetry for Improved through Silicon via Fill

In recent years, semiconductor chips have been shrunk down drastically in order to achieve higher signal propagation, lower power consumption, lower fabrication cost, and reduced form factor, among others. As semiconductor industry struggled to keep up with adding more functionality into smaller and smaller geometries, Moore’s law has finally reached its limitation without new ground-breaking technologies in processing and assembly. Vertical integration, i.e., 3DIC or 3D packaging, has emerged as the most promising technology to achieve the above goals.Silicon interposer, using through silicon via (TSV) becomes a key part of this 3DIC technology evolution. Traditional TSV fabrication involves deep reactive ion etching of silicon via, chemical vapor deposition (CVD) or physical vapor deposition (PVD) of barrier and seed layers inside the via, and electrochemical deposition (ECD) of copper to fill the via. [1]ECD chemistry is arguably the most important factor to deliver a void free, cost effective bottom-up fill with low overburden in the TSV fabrication. Due to the reasons of long process time, tight process windows, and consumption of organic additives in the ECD process, an accurate chemical analysis of the plating bath is essential to control the ECD process, quality and uniformity in via fill.This paper discusses using cyclic stripping voltammetry (CVS) and cyclic pulse stripping voltammetry (CPVS) to control a TSV via fill chemistry. The process window of this chemistry is so tight that a slight imbalance of the additive would result in via fill from a complete bottom up fill to a complete conformal fill, so an accurate correlation of the CVS responses is needed.Fig. 1 is a typical voltammogram in copper virgin makeup solution. Voltage sweep starts at region 1 and goes to region 2 for electrode surface clean. Region 3 is for the organic absorption on electrode surface. Region 4 is for copper deposition. Region 5 is the copper stripping peak.Organic additive such as suppressor will absorb on the electrode surface to minimize copper plating, as shown in Fig. 2. Copper stripping peak current decreases as the suppressor concentration in the solution increases. Accelerator, on the other hand, will compete with suppressor absorption on the electrode surface to cause an increase in the copper stripping peak current.Accelerator analysis is typically done with response curve (RC) method. A response curve is generated by plotting the Ar/Ar0 ratio a range of accelerator concentrations that cover the accelerator concentration in the actual plating bath. Ar is the stripping peak area with addition of accelerator. Ar0 is the stripping peak area in VMS. Plating bath samples are analyzed in the same way by plotting the Ar/Ar0 ratio and finding the corresponding accelerator concentration, as shown in Fig. 3.To cover a wide of accelerator concentrations in the analysis, different standard solutions must be prepared and analyzed. The CVS response is corrected based on the linear regression model from the results of the standard solutions. The corrected values are then plotted against the CVS responses for precision check to ensure that this CVS analysis method can be used to analyze plating bath samples with a wide range of accelerator concentration.In the tertiary organic system the organic additives compete with each other for absorption sites on the electrode surface. The presence of suppressor and leveler will impact the accuracy and precision of the accelerator analysis. The impact of leveler on accelerator analysis is shown in the Fig. 4. In order to get an accurate accelerator analysis, the concentration of leveler must be high enough such that the electrode surface is fully suppressed before addition of accelerator.Accurate and precise chemistry control is essential for manufacturable TSV fill. This paper outlines the methodology for achieving this control.[1] C. Uzoh, et. al., “Deposition Process for Competitive Through Silicon Via Interposer for 3D”, 8th Annual International Wafer-Level Packaging Conference (2012).

PD-L1 enhances CNS inflammation and infarct volume following experimental stroke in mice in opposition to PD-1

BackgroundStroke severity is worsened by recruitment of inflammatory immune cells into the brain. This process depends in part on T cell activation, in which the B7 family of co-stimulatory molecules plays a pivotal role. Previous studies demonstrated more severe infarcts in mice lacking programmed death-1 (PD-1), a member of the B7 family, thus implicating PD-1 as a key factor in limiting stroke severity. The purpose of this study was to determine if this protective effect of PD-1 involves either of its ligands, PD-L1 or PD-L2.MethodsCentral nervous system (CNS) inflammation and infarct volume were evaluated in male PD-L1 and PD-L2 knockout (-/-) mice undergoing 60 minutes of middle cerebral artery occlusion (MCAO) followed by 96 hours of reperfusion and compared to wild-type (WT) C57BL/6J mice.ResultsPD-L1-/- and PD-L2-/- mice had smaller total infarct volumes compared to WT mice. The PD-L1-/- and to a lesser extent PD-L2-/- mice had reduced levels of proinflammatory activated microglia and/or infiltrating monocytes and CD4+ T cells in the ischemic hemispheres. There was a reduction in ischemia-related splenic atrophy accompanied by lower activation status of splenic T cells and monocytes in the absence of PD-L1, suggesting a pathogenic rather than a regulatory role for both PD-1 ligands (PD-Ls). Suppressor T cells (IL-10-producing CD8+CD122+ T cells) trafficked to the brain in PD-L1-/- mice and there was decreased expression of CD80 on splenic antigen-presenting cells (APCs) as compared to the WT and PD-L2-/- mice.ConclusionsOur novel observations are the first to implicate PD-L1 involvement in worsening outcome of experimental stroke. The presence of suppressor T cells in the right MCAO-inflicted hemisphere in mice lacking PD-L1 implicates these cells as possible key contributors for controlling adverse effects of ischemia. Increased expression of CD80 on APCs in WT and PD-L2-/- mice suggests an overriding interaction leading to T cell activation. Conversely, low CD80 expression by APCs, along with increased PD-1 and PD-L2 expression in PD-L1-/- mice suggests alternative T cell signaling pathways, leading to a suppressor phenotype. These results suggest that agents (for example antibodies) that can target and neutralize PD-L1/2 may have therapeutic potential for treatment of human stroke.

Molecular interactions in ribose transport: the binding protein module symmetrically associates with the homodimeric membrane transporter.

The Escherichia coli high-affinity ribose transporter is composed of the periplasmic ribose-binding protein (RBP or RbsB), the membrane component (RbsC) and the ATP-binding protein (RbsA). In order to dissect the molecular interactions initiating the transport process, RbsC suppressors for transport-defective rbsB mutations were isolated. These suppressors are localized in two regions of RbsC, which are allele-specific to N- or C-terminal domain mutations of RBP, suggesting that there are two distinct regions of RbsC, each interacting with one of the two domains of RBP. To demonstrate that these two regions provide a homodimeric binding surface for RBP we constructed a dimeric rbsC in which two genes are joined tandemly from head to tail with the addition of a linker. The dimeric RbsC protein is stable and functional in growth and ribose uptake. By exploiting the allele specificity between the domain-specific mutations and their suppressors, we generated all mutation-suppressor combinations in a single rbsB plus the dimeric rbsC genes. Their phenotypes are consistent with the proposal that the binding protein module interacts symmetrically with homodimeric RbsC. The mode of association proposed here for the ribose transport components could be extended to other ABC transporters with similar structural organizations.

Interactions of ribosome nascent chain complexes of the chloroplast-encoded D1 thylakoid membrane protein with cpSRP54.

The mechanisms of targeting, insertion and assembly of the chloroplast-encoded thylakoid membrane proteins are unknown. In this study, we investigated these mechanisms for the chloroplast-encoded polytopic D1 thylakoid membrane protein, using a homologous translation system isolated from tobacco chloroplasts. Truncated forms of the psbA gene were translated and stable ribosome nascent chain complexes were purified. To probe the interactions with the soluble components of the targeting machinery, we used UV-activatable cross-linkers incorporated at specific positions in the nascent chains, as well as conventional sulfhydryl cross-linkers. With both cross-linking approaches, the D1 ribosome nascent chain was photocross-linked to cpSRP54. cpSRP54 was shown to interact only when the D1 nascent chain was still attached to the ribosome. The interaction was strongly dependent on the length of the nascent chain that emerged from the ribosome, as well as the cross-link position. No interactions with soluble SecA or cpSRP43 were found. These results imply a role for cpSRP54 in D1 biogenesis.

Langerhans cell accumulation in chronic tinea pedis and pityriasis versicolor

Persistence of chronic tinea pedis (CTP) and pityriasis (tinea) versicolor (PIVE) has been tentatively attributed to an impaired cellular immune response. Therefore immunophenotyping of the inflammatory infiltrates in both disorders was performed in order to detect possible defects in cellular defence. The results of the present study show a dominance of memory T cells, an accumulation of macrophages and lack of B cells. A very prominent feature in CTP and especially PIVE was a marked accumulation of Langerhans cells (LCs) in the epidermis, mostly without expression of CD4. Furthermore, reduced expression of cellular activation markers and the presence of suppressor T cells was noted. In general, the cellular response in PIVE appeared to be slightly stronger than in CTP. This composition of the inflammatory infiltrates in chronic dermatomycoses is similar to previous findings in a variety of dermatoses. However, in PIVE and CTP local reduction of delayed-type hypersensitivity may occur. The function of LCs in these infections is therefore of special interest.

Local Suppression of Contact Hypersensitivity in Mice by a New Bifunctional Psoralen, 4,4',5'-trimethylazapsoralen, and UVA Radiation

Although psoralens plus UVA radiation (320-400 nm) have been widely used for the treatment of dermatologic diseases, the toxic effects of these agents have led investigators to develop new photochemotherapeutic compounds. One such compound is 4,4',5'-trimethylazapsoralen (TMAP), a new bifunctional molecule. The purpose of this study was to examine the immunologic side effects of repeated treatment of C3H mice with TMAP plus UVA radiation. During this treatment, the number of ATPase+, la+, and Thy-1+ dendritic epidermal cells greatly decreased in the treated site, despite the lack of phototoxicity. The reduction in the number of detectable cutaneous immune cells was accompanied by a decrease in the induction of contact hypersensitivity to dinitrofluorobenzene applied to the treated skin, an impairment in the antigen-presenting activity of draining lymph node cells, and the presence of suppressor lymphoid cells in the spleen of unresponsive mice. Treatment with UVA radiation alone also reduced the number of ATPase+, Ia+, and Thy-1+ cells in the skin, but did not cause any detectable alterations in immune function. This implies that morphologic alterations in these cells do not necessarily indicate loss of function. Thus, although TMAP in combination with UVA radiation is not overtly phototoxic, it is highly immunosuppressive in mice.

Effects of cyclosporin A on the production of experimental anti-erythrocyte autoantibodies in mice

Mice were treated with cyclosporin A (CsA) (25–100 mg/kg daily, by mouth) during the induction of autoantibodies to erythrocytes by means of injections of rat erythrocytes. A high dose of CsA inhibited autoantibody production whereas a low dose temporarily potentiated it. Cell transfer and anti-Thy 1.2 treatment indicated the presence of suppressor T cells in the spleens of immunized mice. Their formation was inhibited by treatment with high dose CsA and potentiated by low dose CsA. In the CBA/H mice used, CsA treatment after immunization had no effect on autoantibody titres.

SUPPRESSOR CELL ACTIVITY OF CELLS INFILTRATING RAT RENAL ALLOGRAFTS PROLONGED BY PERIOPERATIVE ADMINISTRATION OF EXTRACTED HISTOCOMPATIBILITY ANTIGEN AND CYCLOSPORINE

Suppressor T cells were identified in situ within renal allografts of hosts rendered unresponsive by perioperative administration of donor histocompatibility antigen, which was extracted from donor spleen cells with 3M KCl, combined with cyclosporine (Ag-CsA). Infiltrating cells harvested from Buffalo (BUF, RT1b) renal allografts ten days after transplantation into Wistar-Furth (WFu, RT1u) rats treated with a single i.v. injection of 5 mg 3M KCl-extracted donor antigen (Ag) combined with a three day course of CsA inhibited the mixed lymphocyte culture (MLC) reaction between normal responder WFu and irradiated BUF cells (79.3% suppression, P less than 0.001), but not third-party Brown-Norway (BN, RT1n) stimulator cells (-5.4% suppression, NS). The suppressor effect was not due to cytolysis: the infiltrating cells did not lyse 51Cr-labeled concanavalin A (Con-A) blastoid BUF cells, as did the infiltrating cells from nonimmunosuppressed recipient allografts undergoing rejection responses toward BUF (49% specific cytolysis, E/T = 25), but not third-party BN, target cells five days after transplantation. The suppressor cells were nonadherent to plastic dishes and sensitive to monoclonal antibodies (Mab) W3/13 HLK (pan-T cells: % suppressor -17.9) or cytotoxic/suppressor cells with Mab OX-8 (-5.0% suppression), but not W3/25 (helper; 48.6% suppression, P less than 0.025). Moreover, adoptive transfer of 10(6) infiltrating cells from Ag-CsA-treated recipient allografts into virgin WFu hosts prolonged primary BUF graft survival from 7.2 to 14.0 days (P less than 0.05), but not third-party BN grafts (treated MST = 11.9 +/- 3.9 days versus untreated MST = 11.0 +/- 2.9 days, NS). On the other hand, infiltrating cells from CsA-only-treated recipient allografts could not transfer this effect (MST = 7.7 +/- 0.5 days, P less than 0.01). Finally, retransplantation of the BUF allograft from the Ag-CsA treated rat to a syngeneic, virgin WFu host ten days after primary transplantation yielded prolonged survival with MST 11.4 +/- 2.3 versus control primary graft survival in untreated animals of 7.2 +/- 0.6 days (P less than 0.001). BUF allografts from treated WFu hosts retransplanted into third-party BN rats did not display prolonged graft survival (MST = 9.2 +/- 1.1 days) compared with primary BUF grafts in untreated BN recipients (MST = 9.2 +/- 2.0 days, NS). The presence of suppressor T cells both in the spleen and in situ in renal allografts following Ag-CsA treatment suggests that local mechanisms may augment systemic elements to control the generation of alloimmunity.

Transplantation tolerance: Lyt-1+2- helper T cells require a second proliferation signal to overcome Lyt- 1-2+ suppressor T cell activity.

This study investigated why nude mouse T cell precursors that differentiated in an allogeneic thymus graft were rendered tolerant to alloantigens of the thymus genotype. Our results showed that Lyt- 1-,2+ suppressor T cells inhibited clonal expansion of helper T cells reactive to thymus-donor alloantigens as the mechanism of tolerance. This suppressor T cell activity could be modulated in vitro with either exogenous interleukin 2 (IL 2) or anti-Lyt-1 monoclonal antibody as an IL 2 inducer. Monoclonal antibody stimulation of IL 2 production by primed helper T cells was effective even in the presence of suppressor T cells. These results indicate: i) that alloantigen-specific helper T cells were not defective in their ability to recognize alloantigens of the thymus-donor genotype and to produce IL 2; ii) that Lyt-1-,2+ suppressor T cells prevented Lyt-1+,2- helper T cells specific for the thymus-donor alloantigens from producing IL 2; and iii) that signals delivered through binding of anti-Lyt-1 antibody modulated suppressor activity on alloantigen-primed helper T cells and permitted IL 2 production by these helper T cells. Accordingly, a delicate balance of helper and suppressor T cell activity was required for the maintenance of transplantation tolerance. Furthermore, these results argue against clonal deletion of Lyt-1+,2- helper T cells reactive to alloantigens of the thymic genotype as a mechanism of such transplantation tolerance.

Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin.

Antigen-specific human T cell clones specific for defined peptides of influenza A hemagglutinin were found to be rendered unresponsive by incubation with moderately high concentrations of antigen. This was the case whether the synthetic peptide antigen was present for the duration of the culture or the cloned T cells were preincubated with antigen for 3-18 h at 37 degrees C, before stimulation with T-depleted irradiated sheep erythrocyte non-rosette-forming lymphocytes (E-) pulsed with the optimal dose of peptide. Tolerance could not be overcome by culture with various numbers of E- cells and antigen. The induction of unresponsiveness was antigen specific, since it depended upon incubation with the appropriate peptide recognized by that clone. In addition, the tolerant T cells remained unresponsive to stimulation with the specific peptide for at least 7 d after induction even though maintained in culture in the presence of T cell growth factor. This state of antigen-specific unresponsiveness is akin to immunological tolerance. Furthermore, the experiments reported here demonstrate that the helper T cell clone can be inhibited by the relevant peptide in the absence of any suppressor cells or their precursors. This suggests that antigen-induced unresponsiveness need not always depend on the presence of suppressor T cells. The induction of tolerance in T cell clones does not result in early T cell death, since cells that no longer proliferate in response to the specific antigen and accessory cells still proliferate in response to T cell growth factor.

Cellular and humoral suppressor activity induced by concanavalin A-stimulated human fetal liver cells.

Incubation of human fetal liver cells (HFLC), obtained from 8-12-week-old fetuses, with mitogenic doses of Concanavalin A (Con A) resulted in generation of a population that could suppress alloantigen-induced lymphoproliferation. The supernatant media in which these cells were activated suppressed DNA synthesis, both in mitogen and alloantigen induced peripheral blood lymphocyte cultures. Suppression was achieved only when the Con A-activated cells or the supernatants were added during the early stages of sensitization. Treatment of the cells with mitomycin C after Con A activation did not alter their ability to mediate suppression. This study indicates the presence of suppressor or presuppressor cells in the liver in the early period of fetal life. If the suppressor activity of HFLC in vitro is also induceable in vivo, it may contribute to the fetal defense mechanism against maternal rejection.

Long range control circuits within mitochondria and between nucleus and mitochondria. II. Genetic and biochemical analyses of suppressors which selectively alleviate the mitochondrial intron mutations.

In the preceding paper of this series (Dujardin et al. 1980 a) we described general methods of selecting and genetically characterizing suppressor mutations that restore the respiratory capacity of mit- mitochondrial mutations. Two dominant nuclear (NAM1-1 and NAM2-1) and one mitochondrial (mim2-1) suppressors are more extensively studied in this paper. We have analysed the action spectrum of these suppressors on 433 mit- mutations located in various mitochondrial genes and found that they preferentially alleviate the effects of mutations located within intron open reading frames of the cob-box gene. We conclude that these suppressors permit the maturation of cytochrome b mRNA by restoring the synthesis of intron encoded protein(s) catalytically involved in splicing i.e. mRNA-maturase(s) (cf. Lazowska et al. 1980). NAM1-1 is allele specific and gene non-specific; it suppresses mutations located within different introns. NAM2-1 and mim2-1 are intron-specific: they suppress mutations all located in the same (box7) intron of the cob-box gene. Analyses of cytochrome absorption spectra and mitochondrial translation products of cells in which the suppressors are associated with various other mit- mutations show that the suppressors restore cytochrome b and/or cytochrome oxidase (cox I) synthesis, as expected from their growth phenotype. This suppression is, however, only partial: some new polypeptides characteristic of the mit- mutations can be still detected in the presence of suppressor. Interestingly enough when box7 specific suppressors NAM2-1 and mim2-1 are associated with a complete cob-box deletion (leading to a total deficiency of cytochrome b and oxidase) partial restoration of cox I synthesis is observed while cytochrome b is still totally absent. These results show that in strains carrying NAM2-1 or mim2-1 the presence of cytochrome b gene is no longer required for the expression of the oxi3 gene pointing out to the possibility of a mutational switch-on of silent genes, whether mitochondrial, mim2-1, or nuclear, NAM2-1. This switch-on would permit the synthesis of an active maturase acting as a substitute for the box7 maturase in order to splice the cytochrome b and oxidase mRNAs.

Diamond‐blackfan anemia: The role of immunoglobulin blocking factor in remission

AbstractSome patients with Diamond‐Blackfan syndrome may have suppressor T‐cells responsible for the failure of normal erythropoiesis. The capacity of Diamond‐Blackfan syndrome mononuclear cells to react in mixed leukocyte culture to the stimulus of nucleated red cells was tested using bone marrow as the cell source. In all but one instance, Diamond‐Blackfan mononuclear cells and cells from normal or a multiply‐transfused control showed similar degrees of stimulation. Patient mononuclear cells reacted normally to phytohemagglutinin (PHA). The presence of a cytotoxic effect of Diamond‐Blackfan mononuclear cells on normal nucleated red cells was examined using a 59Fe‐release assay. There was no evidence for lymphocyte‐mediated erythroid cytotoxicity. Immunoglobulins (Ig) were removed from Diamond‐Blackfan serum by affinity chromatography. Erythroid burst‐forming units (BFU‐E) failed to grow normally in Ig‐depleted patient autologous serum, but growth failure was reversed when Ig eluted from the affinity column was added back to the culture. Diamond‐Blackfan Ig added to autologous mononuclear cells in the absence of autologous serum normalized colony growth. T‐cells of some Diamond‐Blackfan syndrome patients may suppress BFU‐E growth, but they do not react abnormally in mixed leukocyte culture to nucleated erythroid cells and are not cytotoxic for erythroblasts under our conditions of study. The serum‐blocking factor in our patients appears to be an Ig that promotes BFU‐E generation despite the presence of suppressor T‐cells. Although it cannot be proved, this may be related to the remission of disease in our patients.

T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor.

The results of this paper are consistent with the hypothesis that progressive growth of the Meth A fibrosarcoma evokes the generation of a T-cell-mediated mechanism of immunosuppression that prevents this highly immunogenic tumor from being rejected by its immunocompetent host. It was shown that it is possible to cause the regression of large, established Meth A tumors by intravenous infusion of tumor-sensitized T cells from immune donors, but only if the tumors are growing in T-cell-deficient recipients. It was also shown that the adoptive T-cell-mediated regression of tumors in such recipients can be prevented by prior infusion of splenic T cells from T-cell-intact, tumor-bearing donors. The results leave little doubt that the presence of suppressor T cells in T-cell-intact, tumor-bearing mice is responsible for the loss of an earlier generated state of concomitant immunity, and for the inability of intravenously infused, sensitized T cells to cause tumor regression. Because the presence of suppressor T cells generated in response to the Meth A did not suppress the capacity of Meth A-bearing mice to generate and express immunity against a tumor allograft, it is obvious that they were not in a state of generalized immunosuppression.

Idiotype suppression. III. Induction of unresponsiveness to sensitization with anti‐idiotypic antibody: identification of the cell types tolerized in high zone and in low zone, suppressor cellmediated, idiotype suppression

AbstractUnresponsiveness of strain A/J mice to sensitization with guinea pig IgG anti‐A5A idiotypic antibody is induced by prior injection of guinea pig IgG2 anti‐A5A idiotypic antibody or unfractionated anti‐A5A antiserum. Two different forms of unresponsiveness could be induced depending on the dose of IgG2 anti‐A5A: high‐zone suppression was maximal one week after injection, could not be transferred by lymphocytes and disappeared within 3 to 4 weeks. Low‐zone suppression took 7 weeks to fully develop and could be transferred by splenic and lymph node T cells.High‐zone suppression is expressed as transient unresponsiveness in both the A5A‐idiotype‐positive T helper as well as B precursor cell compartments. Low‐zone, suppressor cell‐mediated suppression is expressed as chronic unresponsiveness in the A5A‐idiotype‐positive T helper cell compartment only, whereas the A5A‐idiotype‐positive B precursor cells remain fully responsive as revealed by addition of nonsuppressed T helper cells. These data satisfactorily explain that suppression of T helper cell‐independent idiotypes does not involve T suppressor cells. However, since the presence of suppressor T cells is accompanied by selective unresponsiveness of A5A‐positive B cells, the data imply that idiotypic restrictions exist for T‐B cooperation.

Regulation of delayed‐type hypersensitivity I. T suppressor cells for delayed‐type hypersensitivity to sheep erythrocytes in mice

Mice injected with 1 X 10(8) sheep red blood cells (SRBC) into the footpad showed high levels of delayed-type hypersensitivity (DTH) to SRBC 4-8 days after the injection. In contrast, mice injected intravenously with 1 X 10(9) SRBC were unresponsive to DTH induction through 1 X 10(8) SRBC injected into the footpad. This suppression of DTH was maintained for at least 6 weeks and was transferable spleen, lymph node and thymus cells to normal syngeneic recipients. Bone marrow cells, on the other hand, did not contain the suppressor cells. The suppression of DTH was antigen-specific in that DTH to chicken red blood cells and contact sensitivity to 2,4-dinitrofluorobenzene was not affected. The suppressor cells were theta-positive and Ig-negative. They appeared in the spleen in optimum number 3-4 days after induction. The suppressor cells affected both the induction and manifestation of DTH. The presence of suppressor and effector cells for DTH inducible by different routes of antigenic presentation reflects the dynamic balance in the regulation of DTH.

Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. II. Selective inactivation of hapten-reactive suppressor T cells by hapten-nonimmunogenic copolymers of D-amino acids, and its application to the study of suppressor T-cell effect on helper T-cell development.

An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL. Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL. Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.