Modulation of help and suppression in a hapten-carrier system.

Provision of beta-galactosidase (GZ) under defined conditions of dose and time can either help or suppress a subsequent response to trinitrophenyl (TNP)-GZ in CBA/J mice. The optimal helper effect occurs when 10(7) spleen cells from mice primed 9 or more days previously with 10 mug GZ are adoptively transferred to irradiated recipients which are than challenged with 10 mug TNP50GZ. Optimum suppression results from the transfer of spleen cells from mice primed 3 days previously with 100 mug GZ and challenge of recipients with TMP150GZ. Both help and suppression are carrier-specific and mediated by T cells. In experiments where helper or suppressor cells were mixed with normal cells, the anti-TNP response was proportional to the number of primed cells transferred. The results point to a wave of suppression as the initial event after immunization, which is succeeded by period in which the helper effect dominates.     

Regulation of immunoglobulin production in human peripheral bood leukocytes: cellular interactions.

The intercellular influences regulating immunoglobulin (Ig) synthesis by normal human peripheral blood leukocytes (PBL) were investigated in cells stimulated by pokeweed mitogen (PWM). This system was shown to be totally T lymphocyte dependent as purified B lymphocytes (less than or equal to 1% T lymphocytes) failed to make significant amounts of Ig. No evidence was obtained for an Ig class switch as all classes of Ig (IgM, IgG, IgA) were shown to be produced in increasing amounts over a 6-day time period. T lymphocytes demonstrated maximum helper effect when mixed with equal numbers of B cells. This helper effect was mediated through the dual mechanisms of increasing the number of B lymphocytes containing cytoplasmic Ig and by increasing the maturity of these B lymphocytes as demonstrated by an increasing Ig production per B lymphocyte. When present in higher numbers, T lymphocytes were also capable of suppressing Ig production. This T-mediated suppression was first evident as a decrease in the Ig produced per B lymphocyte (decreased maturity). With maximum T suppression Ig-containing B lymphocyte numbers were also diminished. T lymphocyte help was relatively independent of macrophages (phagocytic cells) and did not require DNA synthesis for expression. Both T help and suppression were shown to cross allogeneic barriers. Immature T lymphocytes (thymocytes) were incapable of mediating either activity. Normal human PBL contain T lymphocytes campable of mediating both T help and suppression and the Ig produced by PBL was shown to be the balance of these activities. This balance probably represent the participation of distinct T lymphocyte subpopulations analogous to the T helper (Ly 1+) and T suppressor (Ly 2+, 3+) populations in the mouse.     

Regulation of the activation of cytotoxic T lymphocytes by prostaglandins and antigens

The present study demonstrated the presence of two suppressor circuits in the regulation of the in vitro activation and differentiation of cytotoxic T lymphocytes (CTL); these suppressor circuits were mediated by prostaglandins (PG) and antigens, respectively. In intrinsic suppression, the activation of cytotoxic precursor cells was regulated by the host endogenous production of PG. When the regulation by PG was removed (e.g., using indomethacin), lymphokine-induced cytotoxic cells (LICC) were generated. This activation process can be induced in the absence of antigen or mitogen stimulation. In extrinsic suppression, the presence of antigen induced the generation of antigen-nonspecific suppressor T cells to restrict the expansion of antigen-unrelated cytotoxic lymphocyte clones, whereas the antigen-specific CTL clones were spared. The generation of antigen-specific helper cells further augmented the antigen-specific CTL response. These findings indicate that both antigen specific suppressor T cells and antigen nonspecific suppressor T cells are involved in the regulation of CTL responses. These suppressor circuits not only play an active role in monitoring the activation of CTL clones, they also help to determine the specificity and magnitude of the CTL response.     

Suppressor function of hepatic mononuclear inflammatory cells during murine chronic graft-vs-host disease. I. Macrophage-enriched cells mediate suppression in the liver.

Murine chronic graft-vs-host disease (CGBHD) to minor histocompatibility antigens (B10.D2----BALB/c) is characterized by inflammatory destruction of intrahepatic bile ducts, scleroderma-like skin lesions, and lymphoid involution. Spleen cells isolated from this model proliferate poorly when stimulated with mitogens. Previous reports indicate defective lymphocyte proliferation in this model is the result of active suppression induced by the graft-vs-host reaction in the spleen and is mediated by Thy 1.2-, sIg-, plastic nonadherent, splenic natural suppressor (NS) cells. To determine whether the intense CGVHD in the liver is associated with induction of suppression, we compared the suppressor activity of hepatic and splenic mononuclear inflammatory cells isolated concurrently during murine CGVHD. Both hepatic and splenic MC suppressed the proliferation of mitogen-stimulated normal spleen cells in a non-MHC, non-Mls restricted manner. T cells contributed to the suppressor activity of both populations. However, the suppressor activity of hepatic MC was mediated largely by a macrophage-enriched population of MC while that of splenic MC was mediated largely by NS cells.     

The selective growth of murine newborn-derived suppressor cells and their probable mode of action

Naturally occurring suppressor cells residing in the spleens of newborn mice of less than 5 days old are known to suppress various lymphocyte activities. A population of these suppressor cells can be maintained and expanded in the supernatants derived from Wehi-3 cells. These suppressor cells, designated as Wehi-3-expanded neonatal splenocytes (WENS), can suppress mixed lymphocyte reactions (MLR) and T and B cell mitogen responses without any genetic restrictions. The WENS bear the Ly-5, J11d, and class I molecules. WENS suppression is not mediated through an interleukin 1 or interleukin 2 absorptive mechanism. To achieve maximum suppression of MLR, WENS must be present for at least 24 hr. WENS inhibited the proliferation of Wehi-164 cells but not other tumor cells. The inhibition of Wehi-164 growth was due to the action of natural cytotoxic cells, because WENS lysed Wehi-164 cells but not the natural killer target cell YAC-1. Maximum lysis of Wehi-164 by WENS required 18 to 24 hr. Five WENS cell lines were cultured for more than 6 mo; three of the cell lines lost their capacity to lyse Wehi-164 targets (natural cytotoxicity) and simultaneously lost their natural suppressor activity. The two WENS lines that retained natural cytotoxicity also retained natural suppressor activity. Thus, natural suppressor cells may manifest their suppression through a natural cytotoxicity mechanism.     

The allogeneic effect: the mechanism of allosuppression by Lyt-1, Ia- T cells

The kinetics of allohelp mediated by diffusable factors revealed that help by nonirradiated T cells (TOR) peaked at 48 to 72 hr, followed by a sharp decline if the T cells remained in the cultures. The temporal decrease in help after 72 hr was not mediated by suppressor lymphokines because mixtures of early (24 to 48 hr) and late (120-hr) allogeneic supernatants enhanced help synergistically. Lyt-1, Ia- T cells mediated the temporal decline in help and suppressed allogeneic B cell activation in co-cultures, and this "down-regulatory" activity (allosuppression) was radiosensitive. Help by irradiated T cells (T1000R) increased gradually until it plateaued between 96 and 120 hr. The helper activities of the allogeneic supernatants were directly proportional to their T cell growth factor (TCGF) activities. In addition, their kinetics were identical, and the removal of TCGF from 48-hr allogeneic supernatants by adsorption with TCGF-dependent HT-2 cells depleted both helper and TCGF activities. Help was restored to depleted 48-hr and 120-hr allogeneic supernatants by preparations of TCGF obtained from concanavalin A (Con A)-stimulated FS6-14.13 hybridoma cells that were adsorbed with lipopolysaccharide (LPS)-activated B cells or normal spleen cells (NS), but not with HT-2 cells. These results indicate that allohelp is dependent on TCGF. Moreover, help was dependent on at least one factor in addition to TCGF, because a high level of synergy occurred between TCGF and the "help-deficient" 120-hr allogeneic supernatant. In conclusion, the mechanism whereby Lyt-1, Ia- T cells regulated B cell activation with positive and negative allogeneic effects was through the production and subsequent exhaustion of TCGF, respectively. The production of TCGF and help was radioresistant, but exhaustion of TCGF and suppression was radiosensitive.     

Interleukin-10 contributes development of macrophage suppressor activities by macrophage colony-stimulating factor, but not by granulocyte-macrophage colony-stimulating factor

Macrophages are known to possess suppressor activities in immune responses. To determine the effects of GM-CSF and M-CSF on the expression of macrophage suppressor activities, monocyte-derived macrophages cultured with GM-CSF (GM-Mphis) were compared with those cultured with M-CSF (M-Mphis) for antigen-specific proliferation and interferon-gamma (IFN-gamma) production by lymphocytes. Both GM-Mphis and M-Mphis equally suppressed lymphocyte proliferation, but only M-Mphis suppressed IFN-gamma production in response to purified protein derivative (PPD). M-Mphis, but not GM-Mphis, released IL-10 not only in the course of macrophage differentiation but also in response to PPD after maturation to macrophages. From the results that (i) exogenous IL-10 suppressed IFN-gamma production, but not proliferation of lymphocytes, and that (ii) neutralizing antibody to IL-10 reversed suppressor activities of M-Mphis on IFN-gamma production, but not lymphocyte proliferation, it appeared that IL-10 was the major factor responsible for suppression of IFN-gamma production. Thus, these results suggest that only M-CSF augments IL-10-dependent suppressor activity of macrophages on IFN-gamma production and that both GM-CSF and M-CSF induce IL-10-independent macrophage suppressor activity on lymphocyte proliferation.     

Membrane phenotype of murine effector and suppressor T cells involved in delayed hypersensitivity and protective immunity to herpes simplex virus

The membrane phenotype of T cells involved in delayed hypersensitivity (DH), protective immunity, and suppression of delayed hypersensitivity to herpes simplex virus (HSV) has been determined. T cells from immune lymph nodes transferring DH and antiviral immunity to normal recipients were characterized as Lyt 1+2-. There appeared to be no detectable antiviral role for Lyt 1-2+ cells in the transferred cell suspension. Splenic T cells suppressing the induction of DH to HSV were characterized as being both Lyt 1+2- and Lyt 1-2+ 4 weeks after their induction. At earlier times, i.e., after 7 days, the suppression was mediated solely by the Lyt 1+2- population. Thereafter, a progressive increase in the contribution of the Lyt 1-2+ suppressor was observed. Both the early and later phases of suppression were due to I-J positive cells. The nature of the two suppressor cell types is discussed in relation to suppressor cell "cascades" and to the pathogenesis of herpes simplex virus infection.     

Immunoregulation after thermal injury: sequential appearance of I-J+, Ly-1 T suppressor inducer cells and Ly-2 T suppressor effector cells following thermal trauma in mice

Immunoregulation as a consequence of thermal injury was investigated by using a murine model involving a 30% surface area full thickness burn. Both allogeneic mixed lymphocyte reaction (MLR) and in vitro anti-SRBC responses were depressed from days 3 to 25 post-burn. Suppressor T cells could be identified in both systems between days 5 and 15. On day 5 post-burn, an Ly-1+,2-, I-J+ T cell is responsible for the majority of the suppression observed. This cell behaves like a T suppressor inducer T cell in that it must interact with an Ly-2+ cyclophosphamide-sensitive cell to manifest suppression. On day 7 post-burn, only Ly-1-,2+ suppressor T cells are found which can directly suppress the activity of Ly-1+,2- helper T cells. Thus, these cells behave as T suppressor effector cells. We suggest that feedback suppression is in operation after thermal injury, with functional suppressor inducer cells appearing on day 5 post-burn, leading to the appearance of T suppressor effector cells by 7 days post-burn. Recovery from post-burn immunosuppression occurs by day 25 post-burn and is associated with the appearance of V. villosa-adherent T cells, whose activity antagonizes that of the day 7 post-burn suppressor effector. These cells may represent contrasuppressor T cells, which could play a role in the restoration of immunocompetence after burn injury.     

Ultraviolet radiation-induced immunosuppression of delayed-type hypersensitivity in mice

Ultraviolet (UV) radiation present in sunlight plays a critical role in the initiation and promotion of nonmelanoma skin carcinogenesis and immune suppression. The immune suppressive effects of UV have been identified as a risk factor for skin cancer induction. For these reasons, scientists have focused on elucidating the mechanisms of UV-induced immune suppression to better understand the pathogenesis of skin cancer induction. A hallmark of UV-induced immune suppression is the generation of antigen-specific suppressor T cells. These suppressor cells have been shown to suppress antitumor immunity as well as other cell-mediated responses such as delayed-type hypersensitivity (DTH) reactions. Due to the excessive cost and time involved in traditional UV carcinogenic experiments, scientists have opted to use UV-induced suppression of DTH reactions as a surrogate model. DTH has been, and continues to be, a widely used assay system to measure in vivo immune function. Although somewhat unsophisticated by today's standards, this assay has great advantages because it presents a fast, inexpensive, and reliable model system to help dissect the mechanisms involved in UV-induced immune suppression. Furthermore, the murine model of DTH enables scientists to perform additional procedures, such as adoptive transfer studies with suppressor T cells, which are currently unavailable with human subjects.     

Cooperation between mouse T-cell subpopulations in the cell-mediated response to a natural poxvirus pathogen.

Irradiated CBA anti-DBA/2 cells (10⁶ cells/culture) suppressed the production of effector cells in cultures containing 10⁷ unprimed CBA (responder) and 10⁶ irradiated DBA/2 (stimulator) spleen cells per culture. The suppressive element was cellular and suppression was specific for the stimulating antigen. The suppressive activity resided in the cytotoxic cell population in that both suppressive and cytotoxic activities were found in cells of the same size range, predominantly in T-cells, were produced in response to similar doses of stimulator antigen, and were produced with the same time course following establishment of first sensitization cultures. Eventual suppression correlated with the cytotoxic activity introduced into second sensitization cultures by suppressor cells. The short-term cytotoxic activity and suppressor activity were both highly radioresistant. These studies indicate that the suppressor cells formed in an in vitro mixed lymphocyte culture are cytotoxic to stimulator cells.     

Induced suppression of the efferent phase of contact sensitivity in rats

A study of the immunosuppressive systems of rats has been conducted with special attention to whether suppressor cells can be induced to down-regulate the efferent limb of contact sensitivity. Contact sensitivity (CS)1 was induced in DA rats 5 days after immunization with trinitrochlorobenzene (TNCB). Intravenous pretreatment of naive rats with TNP-coupled syngeneic spleen cells 7 days before sensitization suppressed the induction of CS by 60%. Suppression of the inductive phase of CS could be transferred adoptively into syngeneic rats with spleen cells of such tolerized animals. Cell fractionation studies showed the OX8+ (CD8) T cell population (cytotoxic/suppressor) was responsible for the suppression in the afferent phase of CS. Such cells were incapable of suppressing preexisting CS. To investigate whether suppression could be induced for the efferent phase, spleen and peritoneal exudate cells (PEC) from rats tolerized by administering TNP-spleen cells iv plus epidermal paintings with TNCB were adoptively transferred into recipients sensitized 4 days earlier. Both spleen cells and PEC suppressed the efferent phase of CS but PEC did so more efficiently. Separation of splenic cells revealed the suppressors to be CD8+ T cells. Furthermore, separation of PEC into plastic adherent and nonadherent cells showed the nonadherent (T cell enriched) cells to be noneffective alone. The adherent subpopulation conveyed suppression but did so more effectively upon addition of the T cells. Thus, T cells and macrophages may operate in concert to achieve suppression of the efferent limb of CS. PEC from tolerized rats suppressed performed CS of any specificity but only after the suppressor cells were triggered with the same antigen that induced them. Since both the afferent and efferent phases of CS have now been shown to be suppressable, two separate suppressor mechanisms may be operable in rats.     

Generation of suppressor cells in the response of human lymphocytes to a polysaccharide from Candida albicans

MPPS stimulation of human lymphocytes is characterized by a 2-way cooperation phenomenon, i.e., T help of B cells and B help of T cells. In this system suppressor cells are generated after 6 days of culture. They were characterized as Ia- T cells. Their suppressor activity affected both T and B cell stimulation, and it may involve 2 different mechanisms: direct cell suppression, and interaction with soluble helper factors.     

The distribution of the Qa-2 alloantigen on functional T lymphocytes

The expression of Qa-2 on functional lymphocytes was investigated in vitro and in vivo by using a monoclonal anti-Qa-2 antibody. In vitro treatment of T cells with antibody and complement demonstrated that T cells mediating help or delayed-type hypersensitivity for anti-SRBC responses were Qa-2+. In addition, cytotoxic T cells and either their precursors or cells involved in their generation were Qa-2+, as were anti-HGG suppressor T cells. Panning techniques were also used to show that secondary suppressor T cells were Qa-2+ and that there may be heterogeneity in suppressor T cells defined by Qa-2 expression. In vivo treatment of mice with anti-Qa-2 resulted in decrease in immune responsiveness seen by i) prolongation of skin grafts with either H-2D or I-A differences, ii) suppression of delayed-type hypersensitivity, and iii) inhibition of T cell-mediated suppression. Finally, IgG, but not IgM, anti-body-forming cells were Qa-2+.     

Interferon is the suppressor of hematopoiesis generated by stimulated lymphocytes in vitro

Lymphocytes that inhibit hematopoiesis may have a pathogenic role in some forms of bone marrow failure, and lymphocyte-mediated suppression may also be important in the normal regulation of bone marrow function. We have investigated the mechanism of in vitro suppression of hematopoiesis by T cells by using the methylcellulose colony culture system. Total peripheral blood T cells and separated subpopulations of helper (OKT4+) and suppressor (OKT8+) cells that have been stimulated by exposure to lectin suppress autologous colony formation by bone marrow myeloid (CFU-C) and erythroid (BFU-E) progenitor cells. Medium conditioned by these cells is also inhibitory, indicating that the suppressor activity is a soluble factor. A strong correlation existed for the concentration of interferon and the degree of hematopoietic suppressor activity in these supernatants; both activities peaked at days 3 to 5 of incubation and had sharply declined by day 7. Interferon production was enhanced by exposure of lymphocytes to sheep red blood cells during the rosetting procedure. Specific antiserum and a monoclonal antibody directed against gamma-(immune) interferon abrogated the inhibitory activity for hematopoiesis produced by lectin-stimulated T cells; an antiserum to alpha-interferon was generally much less effective in neutralizing activity. We infer from these results that gamma-interferon is the mediator of hematopoietic suppression generated by lectin-treated T-cells.     

Induction of suppressor cells to T- and B-cell proliferative responses and immunoglobulin production by monoclonal antibodies recognizing the CD3 T-cell differentiation antigen

Monoclonal antibodies (mAb's) recognizing the CD3 T-cell differentiation antigen induced the generation of suppressor cells. These cells inhibited (1) proliferative responses of human peripheral blood mononuclear cells (PBMC) to PHA and allogeneic cells in mixed leukocyte culture; (2) proliferative responses of purified E-rosette-negative cells to Staphylococcus aureus Cowans I; and (3) de novo immunoglobulin synthesis and secretion in the pokeweed mitogen (PWM)-induced differentiation system. Monoclonal antibodies recognizing other T-cell differentiation antigens (anti-Leu 2a, anti-Leu 3a, and anti-Leu 5) did not induce the generation of suppressor cells, even at very high antibody concentrations. Statistically significant differences were not observed in the ability of the OKT3 and anti-Leu 4 mAb's to induce suppressor cells. Monocytes were not required for the generation of anti-CD3-induced suppressor cells. F(ab')2 fragments of the OKT3 mAb's were equally effective when compared with intact antibody molecules in inducing suppressor cells, although they did not induce proliferative responses. Proliferation was not required for the induction of suppressor cells. Irradiation (2500 rad) of PBMC before incubation with the anti-CD3 mAb did not affect the generation of suppressor cells. Furthermore, anti-CD3-induced suppressor cells were radioresistant. Addition of recombinant IL-2 to the cultures of responding cells and suppressor cells did not reverse the suppression. In vitro treatment of anti-CD3-induced suppressor cells with either the OKT4 mAb plus complement or the OKT8 mAb plus complement partially decreased the suppression of proliferative responses of PBMC to PHA or allogeneic cells in mixed lymphocytes culture. However, treatment with both OKT4 and OKT8 mAb's plus complement or the OKT11 mAb plus complement completely abolished the suppression. These results suggest that the suppressor cells are of the T11+T4+T8- and T11+T4-T8+ phenotypes. In other experiments, T4+T8- and T8+T4- cells were isolated from PBMC treated for 48 hr with anti-CD3 mAbs. Both these two populations significantly inhibited proliferative responses of autologous PBMC to PHA and de novo immunoglobulin synthesis and secretion by mixtures of purified T4 and B cells from normal donors, in the PWM-induced differentiation system. These results demonstrate that anti-CD3-induced suppressor cells are of the T4 or T8 phenotype. Treatment of purified T4+T8- and T8+T4- cells with anti-CD3 mAb's resulted in the generation of suppressor cells, suggesting that the precursors of the anti-CD3-induced suppressor cells can belong to either of these two populations.(ABSTRACT TRUNCATED AT 400 WORDS)     

The helper and suppressor functions of primate T cells elicited by a 185K streptococcal antigen, as compared with the helper function elicited by a 4K streptococcal antigen

Helper and suppressor functions of human T lymphocytes that act on antibody-forming B cells were elicited by a large 185K streptococcal cell wall antigen. However, a small 4K streptococcal peptide elicited helper but no suppressor function. These differences in the functional activities of the large and small m.w. streptococcal antigens (SA) were confirmed by direct immunisation of rhesus monkeys with the 185K-SA and 4K-SA. Sequential studies have shown that whereas the 185K-SA elicits dose-dependent helper and suppressor activities, the 4K-SA elicits only helper function. Cell-depletion studies with human cells suggest that removal of T8+ cells by killing with OK.T8 and complement leads to a loss of suppressor and a broadening in the concentration of 185K-SA, which elicits helper activity. Because the 4K-SA does not elicit suppression, removal of T8+ cells does not affect this function. However, similar depletion of T4+ cells results in loss of the helper activities, both with the 185K-SA and 4K-SA, and again a broadening in the concentration of the 185K-SA, which elicits suppression. Direct comparison by autoradiography between 125I-labeled 185K-SA and 4K-SA suggests that both antigens can bind directly to monocytes or T8+ VV+ cells. Furthermore, both antigens can induce helper function if T4+ cells are reconstituted with either monocytes or T8+ VV+ cells. Attempts will now be made to sequence the amino acid determinants of the 185K-SA, so as to define the epitopes responsible for the two major regulating functions elicited by this antigen.     

Direct in vitro evidence for different susceptibilities to 4-hydroperoxycyclophosphamide of antigen-primed T cells regulating humoral and cell-mediated immune responses to sheep erythrocytes: a possible explanation for the inverse action of cyclophosphamide on humoral and cell-mediated immune responses

Suppressor T cells of humoral immune responses, effector T cells mediating DTH, suppressor T cells of DTH, and helper T cells of humoral immune responses, all with specificity to SRBC, were produced in mice. The biologic activity was tested in adoptive transfer experiments. In vitro treatment with different doses of 4-hydroperoxycyclophosphamide (4-HPCy) yielded the result that the various activities tested were not uniformly sensitive to the action of this drug: Suppressor T cells of humoral immune responses and effector T cells mediating DTH were resistant to doses of 4-HPCy that eliminated the activities of suppressor T cells of DTH and helper cells of the humoral immune response. These findings help to explain the various effects cyclophosphamide has on the in vivo immune response and may help to form a basis for the rational manipulation of the immune response by drugs that selectively affect different subgroups of immune cells.     

Proliferative and cytotoxic immune functions in aging mice. IV. Effects of suppressor cell populations from aged and young mice

The changes with age in three splenic suppressor cell populations were studied in C57BL/6 mice. Allospecific Ts cells and nonspecific non-T suppressor cells were both generated in vitro in allogeneic MLC. The presence of "pre-existing" suppressor cells in fresh spleen cells from normal mice was examined. Suppressor cell activities were assayed for their ability to suppress proliferation in a fresh allogeneic MLC after treatment to prevent their own proliferation. The ability to generate both specific and nonspecific suppressor cells decreased with age, whereas pre-existing suppressor cells were detected in spleens from the majority of the aged animals but not in spleens from young animals. The decrease in suppressor cell activity was not due to any requirement for age matching between donors of suppressor and target cells. The specific and nonspecific MLC-generated suppressor cells inhibited both the proliferative response in the assay MLC and the generation of cytotoxic cells. The pre-existing suppressor cells only suppressed the proliferative response and not the generation of cytotoxic cells. The changes seen with age in these suppressor cell populations suggest that the ability to generate suppression (both allospecific and nonspecific) to newly encountered Ag declines with age, whereas a resident splenic suppressor cell population accumulates over the lifetime of the animals.     

Peptic fragments of bovine serum albumin bind antigen-specific T suppressor cells from orally tolerized mice

The antigenic structures capable of binding immunoregulatory T cells have been investigated. The functional properties (suppression or help) of BSA-specific T cells from primed or orally tolerized mice with capacity to adhere to bovine serum albumin or its peptic fragments were examined in reconstitution experiments in which splenic T-cell populations together with naive B cells were transferred into irradiated syngeneic recipients. Antigen-specific T suppressor cells isolated from mice tolerized to BSA adhered to peptic fragments of BSA as well as to the intact antigen. BSA-specific T helper cells adhered only to the intact antigen. Our data suggest that the preferential activation of T suppressor cells following administration of peptic fragments may be due to their ability to adhere to such fragments. These findings offer a novel approach of separation and identification of T suppressor cells and may be useful in further studies of immunosuppression.