An immunosuppressive factor interacts with membrane glycolipid asialo-GM1 structure.

An immunosuppressive factor was isolated from sheep-erythrocyte hyperimmunized mouse serum. Possibilities of the adsorption of the immunosuppressive factor with glycolipid asialo-GM1 incorporated liposome (dipalmitoyl lecithin) and the blockade of immunosuppressive activity by specific anti-asialo-GM1 incorporated antibody were tested. We report here that: The immunosuppressive activity of the immunosuppressive factor decreased quantitatively if the factor was preincubated with asialo-GM1 incorporated liposome (GALP) as compared with that preincubated with liposome (LP) alone; and the presence of specific anti-asialo-GM1 antibody is able to protect in vitro anti-sheep erythrocyte (SRBC) response from the suppressive effect of the immunosuppressive factor in a dose-dependent fashion under similar cell culture condition. The results indicate that asialo-GM1 may be related to the receptor of immunosuppressive factor.

Correlation between immunosuppressive activity and translation regulatory activity.

An immunoglobulin negative material from the eluate of an anti-idiotype immunosorbent column [1] exhibited potent immunosuppressive activity. This material also inhibited the translation of globin mRNA in a cell-free reticulocyte lysate system. The translation inhibitory activity of this material was not attributable to nucleases which were separable by a blue-dextran agarose column. Further correlation between immunosuppressive activity and translation inhibitory activity was observed when GTP or GTP analogue was included in experimental systems. These results suggest that the immunosuppressive factor (or factors) may contain a translation inhibitory factor. The biochemical mechanism of immunosuppression is discussed.

The effect of febrile temperatures on biologic actions of interferons: abrogation of suppression of delayed-type hypersensitivity and antibody production.

Interferons (IFN) have a complex immunoregulatory effect on all cells of the immune system. In most cases in which IFN had an enhancing effect, the suggested mechanism was inhibition of the generation or activity of suppressor cells. In the present study, we examined the effect of IFN on suppression of the delayed-type hypersensitivity (DTH) response. Suppression was induced with a low antigen dose of sheep erythrocytes (SRBC), and IFN was found to abrogate both the suppressed state and the transferability of this state. Cyclophosphamide had the same effect. However, the in vitro generation of suppressor cells was not altered by the addition of IFN to the culture medium at a normal temperature (37 degrees C). To reconcile the disparity between the successful anti-suppressive action of IFN in vivo compared with its failure in vitro, we considered the possibility that the pyrogenic action of IFN in vivo might create the optimal thermal environment for its anti-suppressive action. Indeed, when IFN was then tested in vitro at a febrile temperature (39.3 degrees C), it completely blocked the generation of suppressor cells. On the other hand, once suppressor cells were generated at 37 degrees C, IFN had no effect on their ability to suppress a fresh culture either at 37 degrees C or at 39.3 degrees C. IFN also had no effect on the generation of helper cells at either temperature, but help was greatly enhanced by high temperature alone. In vivo, we found our IFN preparation to be pyrogenic and observed that an anti-pyretic drug given before and during antigen stimulation abrogated the anti-suppressive effect of IFN. We suggest, therefore, that the febrile state induced by IFN promotes its action on suppressor cells.

Antigen-specific T contrasuppressor factor in cell-mediated immunity: interactions leading to eradication of the tolerant state.

Interactions between a T cell-derived, antigen-specific, contrasuppressor factor (TcsF) and immune T cells that block the action of T suppressor factors and allow the transfer of cellular immunity into tolerant recipients are described. Immune T cells from contact-sensitized donors are capable of transferring specific immunity into normal recipients but not into animals rendered tolerant to the specific antigen. Brief exposure of the immune cells to the TcsF enables the effective transfer of immunity into such tolerant recipients. In addition, treated immune cells become resistant to subsequent exposure to T suppressor factor (capable of inhibiting transfer of immunity to normal recipients). A cyclophosphamide-sensitive, I-J+, Ly-2 T transducer cell is required in the immune donor cell population for contrasuppression to be induced by the TcsF plus specific antigen. These cells release an antigen-non-specific contrasuppressive factor capable of rendering immune targets, depleted of transducer cells, resistant to suppression (either by suppressor factor or in the tolerant recipient). The results indicate that contrasuppression in contact sensitivity is antigen specific and that the balance of suppression and contrasuppression determines tolerance vs responsiveness in this system. The symmetrical resemblance of the contrasuppressive interactions to those of suppression in contact sensitivity are discussed.

Production of antigen-specific contrasuppressor cells and factor, and their use in augmentation of cell-mediated immunity.

A single injection of TNP-labeled mouse gamma-globulin (TNP-IgG) can render the contact sensitivity response of mice resistant to suppressor cells (Tsc) and their biologically active cellfree products (TsF). Lyt-1 T cells of mice treated with TNP-IgG can protect the adoptive contact sensitivity response of immune cells from the antigen-specific suppressive effect produced by the addition of antigen-specific TsF or Tsc. When T cells of TNP-IgG-treated mice are put into culture, they produce an antigen-specific contrasuppressor factor (TcsF) that can replace the activity of the cells. When immune cells are preincubated in vitro with TcsF, they become refractory to Tsc and TsF added subsequently. The TcsF, however, has no ability to restore responsiveness to immune cells that had been previously exposed to TsF. The TcsF binds specifically to TNP, expresses an I-J-controlled determinant, and does not express standard determinants found on mouse Ig. The treatment that primes the contrasuppressor system to protect the contact sensitivity response also reportedly renders the antibody-producing system tolerant, (i.e., produces so called "split tolerance"). These results are discussed in light of the possibility that the contrasuppressor system can be responsible for so called isotype-specific immunity by rendering one arm of the immune system resistant to generalized suppressive mechanisms.

Thymus-derived lymphocytes and their interactions with macrophages are required for the production of osteoclast-activating factor in the mouse.

A bone-resorbing factor, comparable to the osteoclast-activating factor (OAF) produced from peripheral blood leukocytes, is shown to be produced by murine spleen cells activated with the T-cell mitogen Con A. Murine OAF is demonstrated here as being a product of the interaction between thymus-derived T lymphocytes and macrophages. Activation of T cells in the presence of macrophages with Con A yields culture supernatants with OAF activity. This OAF activity is not dialyzable and is not extracted by lipid solvents. Purified B cells in the presence or absence of macrophages and cocultured with Con A or activated with the B-cell-specific mitogen lipopolysaccharide yield culture supernatants with no detectable OAF activity. Similarly, macrophages cocultured with Con A or activated with lipopolysaccharide fail to yield culture supernatants with bone resorbing activity. These types of immune cell interactions are similar to that required for the production of lymphokines. These data support the hypothesis that one aspect of regulation of bone remodeling is through cells of the immune system.

Regulation of B cell lymphomagenesis by a malignant Qal+ inducer T cell clone.

A series of Thy-1.2+ Ly-1+ Qa-1+ malignant T cell clones have been isolated from murine sarcoma virus-murine leukemia-Moloney (MSV-MuLV-M)-induced B cell lymphomas or from MSV-MuLV-M-infected B6 mice. These T cell clones enhance both antigen-independent and -dependent lymphocyte differentiation and function. They also induce the differentiation of granulocytes and erythrocytes in the stem cell compartment, a function that parallels the immunopathology of the disease in vivo. The malignant T cell appears to sustain B lymphoma growth in vivo by releasing a factor (BCGF) that promotes B cell proliferation.

Analysis of hapten-specific T suppressor factors: genetic restriction of TsF1 activity analyzed with synthetic hybrid suppressor molecules.

We have analyzed the first-order suppressor factor secreted by an azobenzenearsonate (ABA)-specific T suppressor cell (Ts) hybridoma. Treatment of the factor with 5 mM dithiothreitol (DTT) yields two fragments with distinct phenotypes and functional capabilities. One fragment is bound by a monoclonal anti-I-J antibody, the other is not. Further, although neither molecular fragment by itself is sufficient to suppress an ABA response, a mixture of the two reconstitutes the suppressive activity. The I-J- portion of the first-order suppressor factor (TsF1) presumably guides the antigen specificity; activity of the ABA-specific Ts I-J- TsF1 factor can be reconstituted with an I-J+ subunit of a TsF molecule of either sheep red blood cell (SRBC) or ABA specificity. The genetic restriction for Igh-linked determinants of the ABA/SRBC hybrid TsF molecules is influenced by the I-J+ portion, regardless of the original antigen specificity of that molecule. The data support a two-subunit TsF model. Polyclonal ABA-specific TsF1 molecules appear to resemble the monoclonal factor in structure.

Distinctive immunological properties of cultured murine thymic epithelial cells.

Skin painting with chemically reactive haptens induces a hapten-specific state of hypersensitivity that is long lasting and can be transferred to unirradiated recipient mice. A similar state of hapten-specific contact sensitivity can be induced by intravenous immunization with hapten-conjugated cells. Thus far, only two cell types have been described that can perform this function: Langerhans cells of the skin, and splenic dendritic cells. All other types, coupled with hapten, induce either tolerance or a short-lived state of contact hypersensitivity that is readily suppressed, and cannot be transferred to normal recipients. In the present experiments, it was demonstrated that culture-enriched, hapten-coupled thymic epithelial cells can also induce a state of stable contact hypersensitivity identical to that induced by skin painting. This provides evidence that thymic epithelial cells have distinctive properties as antigen-presenting cells in vivo. The relationship of this finding to the postulated role of thymic epithelium in T-cell development is discussed.

Contrasuppression: the second law of thymodynamics, revisited.

The data discussed here touch upon several issues in the evolving story of T cell contrasuppression, the underlying theme being that of heterogeneity. First, there is the issue of function. We are considering here only those cells that affect the function of secretory differentiation. We have evidence that different contrasuppressor cells exist for clone growth, but have not yet studied them in the same depth as those for secretory differentiation. Second, there is the important issue of target cells. In this article by Green and Gershon it is pointed out that there is clear evidence that contrasuppressor effects can work by protecting helper cells from suppressor cell effects in vitro. On the other hand, direct additional inhibition of the suppressor cells themselves has not been excluded. The latter point is also true in our system. However, we must suppose for the sake of simplicity in many of our experiments that if suppressors are not the target of the contrasuppressor effects then the B cells themselves probably are. This is because the tumor cells engage in a spontaneous rate of growth and differentiation in the absence of help or suppression. When T cell-dependent, specifically triggered effects reduce this spontaneous behavior, then a suppressive effect must have been delivered directly to the B cells. This is a simplifying assumption which is attractive, but since the experiments are carried out in vivo and thus may be affected by some factors that we have not yet recognized, we are not confident on its "intuitive" appeal. A third issue revolves around triggering specificity. One of our contrasuppressors exhibits the phenomenon of carrier crossreactivity (CRCS) and is thus behaving in accord with expectations aroused by Green and Gershon in this review. The other cell is apparently quite carrier specific (SCS). The meaning of this is not at all clear, but its potential significance may somehow be related to a sort of "mirror image" relationship of the two cells. Thus, for example, in other experiments not discussed here, we have noted that the CRCS binds to 315 protein-coated plates, but as noted here counteracts a suppressive effect which is generated by cells which do not adhere to these plates. In contrast to SCS does not bind to 315 plates and yet, as noted here, appears to counteract a suppressor effect generated by cells which do adhere to 315 plates.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquisition of paralytic activity by inducer cells.

Clones of inducer cells activated by antigen and class II major histocompatibility complex (MHC) gene products synthesize large amounts of several distinct mRNA species not detected in other activated cell types, including antigen-activated suppressor or killer cell clones. Although inducer cells continued to synthesize and secrete peptides at about the same rate for 5 days after activation by adherent cells and antigen, they expressed a new set of mRNAs approximately 3 days after activation. We therefore tested the functional activity of purified Ly1 cells at different days after activation by adherent cells and antigen. We wished to find out (a) whether there was a qualitative or quantitative change in the level of inducer activity, and if so, (b) whether this functional change was an intrinsic property of Ly1 cells or, rather, was dependent on signals from the cellular environment, in particular from adherent antigen-presenting cells. We incubated purified Ly1 cells and splenic adherent cells for 1-7 days in vitro, and tested inducer activity in cultures containing highly purified B cells and sheep erythrocytes (SRBC). Anti-SRBC plaqueforming cells were counted 5 days later. We found that inducer cells that have been incubated with adherent cells in culture for more than 72 h (a) did not induce B cells to produce antibody, and (b) prevented virgin but not immune B cells from receiving T-helper signals. We term this latter phenomenon "paralysis." Acquisition of the ability to paralyze virgin B cells required an I-E gene-regulated interaction between inducer cells and in vitro-activated adherent cells. This interaction did not require antigen and was associated with transition from Ly1:Qa1- to Ly1:Qa1+ cell-surface phenotype. Taken together these findings indicate that (a) interactions between inducer cells and adherent antigen-presenting cells result first in classical inducer ("helper") activity and later in expression of paralytic activity and (b) sequential expression of these inducer activities depends on two distinct signals, supplied by resting and activated adherent cells, respectively. The signal supplied by autologous activated adherent cells is regulated by I-E gene products and is independent of corecognition of foreign proteins. The physiologic significance of this paralytic inducer activity in the prevention of potentially harmful immune reactions to foreign microbial agents is discussed.

B cell-deprived mice lack functional expression of certain T suppressor cell subsets.

The generation of functionally active immunoregulatory T lymphocytes has been shown to depend upon the interaction of a number of different immune cell types during development. In order to understand and perhaps manipulate immunoregulatory T cell interactions, it is important to identify the nature and role of these cell types in the immunoregulatory T cell pathway. We have investigated the role of Ig+ B cells in the generation of suppressor T lymphocytes in the immune response to SRBC. Our approach was to suppress the expression of Ig+ B cells in experimental mice by continuously treating these animals with a rabbit anti-mu-chain antiserum. These animals were simultaneously tested for their ability to make suppressor T cell responses as measured by the ability to produce or accept SRBC-specific suppressor T cell factors. This particular approach, neonatal suppression with anti-mu-chain antibody, has been previously shown to be an effective means of depleting animals of Ig+ cells, while having little or no effect on a number of different T cell-mediated responses, including T cell mediated allograft rejection and delayed-type hypersensitivity responses in vivo as well as the generation of MLR and CTL responses to alloantigens and conventional I-A recognizing T helper cell responses in vitro. Our results indicate that anti-mu-treated mice lack the ability to produce both Ly1 and Ly2 cell-derived suppressor factors when immunized with the relevant antigen SRBC. Further, while the T cells from anti-mu-treated mice were capable of generating a T helper cell response to SRBC in vitro, these T cells no longer responded to suppressor cell signals from either the Ly1 or Ly2 T cell-derived suppressor factors. The ability to produce or accept suppressor cell signals was traced to the lack of an I-J+ Ly1 T cell absent in anti-mu-treated mice. This cell produces an I-J+ antigen nonspecific molecule which imparts Igh-V linked genetic restrictions to both the Ly1 and Ly2 T cell derived suppressor factors. The results alter our view on immune regulation by suggesting that both the induction and effector phase of suppressor T cell activity to SRBC is dependent upon an antigen nonspecific Ly1 I-J+ T cell which is distinct from the antigen recognizing I-J- T cells required for antigen-specific suppression. This I-J+ T cell, which imparts an Igh-linked restriction to the suppressor factors, is critically dependent on Ig+ B cells to reach a functionally active state.(ABSTRACT TRUNCATED AT 400 WORDS)

Regulation of in vitro cytotoxic T lymphocyte generation. III. Interactions or regulatory T cell subsets in suppressor and target populations.

During allogeneic mixed leukocyte cultures (MLC), cytotoxic T lymphocytes (CTL) and at least two kinds of suppressor T lymphocyte (Ts) functions are induced. One Ts, termed nonspecific (TsN), can suppress the in vitro generation of CTL when it is transferred to any allogeneic MLC. The other Ts has specificity for MLC in which stimulator cells are homologous at the major histocompatibility complex (MHC) with stimulator cells used to induce the Ts (TsS). Previously, we have shown that addition of a 10(-4)M concentration of the histamine1 antagonist pyrilamine to the MLC strongly influences the kind of T cell function generated. That is, the generation of CTL and TsN are inhibited while the induction of TsS is not. CTL precursors are activated (CTL-PA) in such cultures, as witnessed by their differentiating in such cultures, as witnessed by their differentiating into CTL effectors upon removal of pyrilamine and transfer to a salubrious environment (e.g., any fresh MLC). This second step in the differentiation of CTL can be prevented by exposure of pyrilamine-treated MLC derived cells to greater than or equal to 500 rads gamma irradiation. Therefore, by using these combined in vitro manipulations, under the proper experimental conditions, it is possible to study TsS in the absence of both TsN and CTL. In the present studies we have used antibodies to the cell surface alloantigens Lyt 1, Lyt 2 and TL/Qa-1 to ask whether TsN and TsS also can be separated by virtue of their having different cell surface phenotypes. In addition, we have explored for the existence of interactions between subsets of T cells in the suppression of CTL generation, and whether these interactions (circuits) are akin to those previously demonstrated to be important in the regulation of B cell responses to antigen. Since CTL generation likely is important in the host defense against viruses and other pathogens, neoplasms, and transplants of foreign tissues, a firm understanding of regulatory interactions modifying this response is important. Our experimental approach has involved a technique found to be successful in the dissection of T cell regulation of B cell responses, i.e., negative selection with alloantigen-specific antibodies and complement (C'). We have found that immune Lyt 1+2+ (Ly 123) T lymphocytes are strongly involved in MLC-induced nonspecific suppression, but are not required for the expression of specific suppression. Rather, both immune Lyt 1+2- (Ly 1) and Lyt 1-2+ (Ly 2) T lymphocytes appear to be involved in optimal TsS function.(ABSTRACT TRUNCATED AT 400 WORDS)

Purification and characterization of TNP-specific immunoregulatory molecules produced by T cells sensitized by picrylchloride (PC1F).

T cell-derived TNP-specific factors associated with immunoregulatory activity were obtained by culture of T cells obtained from mice sensitized by skin-painting with picrylchloride. Culture medium was absorbed to TNP-Sepharose and TNP binding proteins were prepared by elution with TNP. The hapten affinity-purified proteins were characterized by size and charge and were found to be acidic 70,000 m.w. polypeptides that occur as monomers or oligomers. Oligomeric proteins interact with factors produced by mice injected with trinitrobenzenesulfonic acid to form factors that suppress specifically the ability of TNP-sensitized T cells to transfer contact sensitivity to TNP. Monomeric (no more than 70,000 m.w.) molecules do not form suppressor factors but can transfer contact sensitivity to TNP. Moreover, reduction and alkylation of oligomeric molecules inactivates their suppressor activity but causes them to be able to transfer contact sensitivity. The results suggest that T cell-derived antigen-specific molecules may have different effector functions dependent on their oligomeric state.

Mechanisms of suppression in the transfer of contact sensitivity. Analysis of an I-J+ molecule required for Ly2 suppressor cell activity.

The passive transfer of contact sensitivity (CS) by immune cells can be inhibited with an antigen-specific T suppressor factor. This factor is composed of two subfactors: an antigen-specific subfactor made by an Ly1+ cell (PC1-F) and a antigen nonspecific subfactor made by an Ly2+ T cell (TNBSA-F). The suppressive activity of the complete factor can be eliminated by depleting the assay population of Ly2+ cells, even though it is the Ly1+ cell in the population that transfers the adoptive immunity. This suggests that the Ly2+ cell in the assay population is needed to transduce the suppressive signal to the Ly1+ effector cell of DTH. We found that an Ly2+ cell from immune animals could be induced to produce a cell free subfactor that overcame the requirement for this Ttrans cell in the suppression of CS by TsF. The induction required only PC1-F, TNP-coupled spleen cells, and resulted in the production of an antigen-nonspecific I-J+ subfactor by immune Ly2+, I-J+ cells. The need for the Ly2+ transducer cell could also be overcome by addition of an I-J+ molecule secreted by Ly1 T cells hyperimmunized to SRBC. A suppressor complex made from mixing the I-J+ molecule with TNBSA-F could directly suppress the functional activity of immune T cells not only to transfer CS, but also to deliver help to B cells in an in vitro PFC response. This suppressive complex is antigen-nonspecific and does not require Ly2+ T cells in the assay population for suppressive activity. These results indicate that effector factors of the suppressor circuit require two molecules; one that contains the functional suppressor material and one that serves as a "schlepper," a molecule needed to deliver the suppression to the appropriate target cell. The ability to construct a functional suppressor complex from two subfactors raised against different antigens, using different immunization procedures, which were isolated from factors exhibiting different functional activities suggests that certain cells of the immune system may play a universal role in "transducing" the suppressive signal.

Igh variable region-restricted T cell interactions. Genetic restriction of an antigen-specific suppressor inducer factor is imparted by an I-J+ antigen-nonspecific molecule.

Immunized Ly-1 T cells secrete an antigen-specific molecule that will induce Ly-2+ T cells to express suppressive activity. In two separate systems, factors that suppress the primary anti-sheep erythrocyte (SE) plaque-forming cell response of spleen cells in vitro (Ly-1 TsiF) or the contact sensitivity of azobenzenearsonate (ABA)-TsF1 consist of two macromolecules, one which binds antigen and is IJ-, the other which is I-J+ and does not bind antigen. Both of these chains are required for the factor's biological activity. These factors show a genetic restriction in their ability to induce suppression that is linked to the variable region of the Ig heavy chain gene complex (Igh-V). The I-J+ chain from the ABA-specific TsF1 could replace the I-J+ chain needed by the SE-specific Ly-1 TsiF for biological activity. Mixtures of ABA-binding chain with I-J+ material obtained from the SE-specific Ly-1 TsiF had no effect on the primary anti-SE response in vitro. In mixtures of SE antigen-binding chain from Ly-1 TsiF and I-J+ material from the ABA-specific TsF1, it is the I-J+ molecule that determined the factor's Igh-V restriction. Thus, the antigen-combining site of the factor determined the antigen specificity of this factor but is irrelevant to its Igh-V-linked genetic restrictions. The implications of these results for the idiotype network hypothesis are discussed.

Role of Ly-1:Qa1- and Ly-1:Qa1+ inducer T cells in activation of Ly-23 effectors of suppression of antibody production in mice.

Ly-2+ effectors of T cell-mediated suppression require inducing signals from antigen and a helper cell bearing the Ly-1+:Qa1+ surface phenotype. In this report, we have further examined the helper cell requirements for suppressor cell induction of antibody production in mice. By using the T cell subset education procedure in vitro, we have activated T cells to sheep red blood cells (SRBC) antigens and then purified Ly-2 cells before testing for suppressor activity in assay cultures of defined T and B cell subsets. We have confirmed our previous observations that Ly-1+:Qa1+ cells are required for activation of T suppressors, but have found that under the appropriate conditions, there is not a strict requirement for the Ly-123 subset of T cells. Furthermore, if Ly-23 cells are stimulated in the presence of Ly-1+:Qa1- T cells, effective suppressors can be obtained only if a source of Ly-1:Qa1+ inducers is added to the assay culture. If Ly-23 cells are activated by antigen in the absence of Ly-1 cells, subsequent exposure to the Ly-1+:Qa1+ subset under the conditions tested here is not sufficient to activate suppressors. These results show that effectors of suppression, like B cells and cytotoxic T lymphocytes, may respond to two helper cells.

Role of contrasuppression in the adoptive transfer of immunity.

The data presented in this paper show that the population of cells that adoptively transfer contact hypersensitivity are Lyt-1+ 2-, I-J- and nonadherent to V. villosa lectin. However, the adoptive transfer of immunity by this population of cells is successful only when the recipient has been treated in such a way as to impair the host immunosuppression mechanism. This population cannot, on its own, transfer immunity to adult, untreated naive recipients unless an additional population of immunoregulatory cells is present. This immunoregulatory population does not itself adoptively transfer immunity. This latter population is differentiated from the immune cells in that they are Lyt-1+ 2-, I-J+ and are adherent to V. villosa lectin. Both populations are required to adoptively transfer immunity to adult untreated naive recipients.

Ontogenic development of contrasuppression.

Using a xenogeneic graft-versus-host assay system, we have been able to document the sequential appearance of certain regulatory cells in newborn mice. Before birth, mouse spleen cells exhibit potent suppression that cannot be ameliorated by contrasuppressor cells. On the day of birth, the spleens contain equally potent suppressor cells, but these cells now can be inhibited totally by contrasuppressor cells. Between days 1 and 2 after birth, suppression, as picked up by our system, has disappeared. However, it can be found hiding behind contrasuppressor cells, as elimination of the latter cells with appropriate antisera reveals cells with the same suppressive potency as spleen cells taken 1 or 2 days earlier. Further, if the thymus is removed on the day of birth or 1 day later, the suppressor-obscuring cells do not appear. Thus, there appears to be an inherent ontogenic schedule that the thymus follows, which determines the time when different regulatory cells will emerge from it.

Definition of two pathways for generation of suppressor T-cell activity.

Antigen-stimulated Ly1 cells induce T cells from nonimmune donors to develop potent feedback suppressive activity. Suppression is mediated by Ly23 suppressor T (Ts) cells, which are generated from either Ly23 or Ly123 precursors. Ts activity generated from Ly23 precursors requires a strong inducer signal and is rapidly expressed but short lived. In contrast, Ts activity from Ly123 precursors is relatively long lived and is efficiently generated by relatively low levels of inducer signals. Induction of both Ly123 and Ly23 precursors to become Ts cells requires that both cells share genes linked to the Ig-H locus.