Con A-induced Suppression Research Articles

Changes in cell-mediated immune responses after experimentally-induced anaphylaxis in dogs

Experimentally-induced type 1 hypersensitivities were induced in normal dogs to either ovalbumin or Ascaris antigen. In vitro and in vivo cell-mediated immune responses were measured before sensitization and again at 1 and 6 days after induction of anaphylaxis by intravenous challenge with antigen. Histamine-modulated lymphocyte functions, such as histamine-induced suppression, histamine co-mitogen induced blastogenesis and the in vivo cutaneous responses to intradermally injected mitogens decreased post anaphylaxis. Spontaneous suppression of the autologous mixed-lymphocyte reaction increased post anaphylaxis. Lymphocyte blastogenic response to Concanavalin A (Con A) decreased at 6 (but not at 1) days post anaphylaxis probably due to a mediator other than histamine. Blastogenesis of 24 h preincubated cells by suboptimal concentration of Con A, declined post anaphylaxis, but Con A-induced suppression was not significantly altered. Dogs with atopic dermatitis have some altered cell-mediated immune responses. Altered histamine-induced and spontaneous suppression, histamine suppression of mitogenesis and decreased contact sensitivity observed in this experimental type 1 hypersensitivity mimicked that of atopic dogs. Increased cutaneous response to mitogens observed in atopic dogs was not reproduced in the type 1 hypersensitive dogs. These findings suggest some of the altered cell-mediated immune functions observed in dogs with atopic dermatitis result from type 1 hypersensitivity. The other abnormalities may be intrinsic to the atopic state.

Altered spontaneous and histamine-induced in vitro suppressor-cell function in dogs with atopic dermatitis

Spontaneous, histamine-induced and Concanavalin A (Con A)-induced suppression of Con A mitogenesis of autologous responder cells was studied in normal dogs and in dogs with atopic dermatitis. Histamine-induced suppression was significantly decreased in the atopic dogs, as was the Con A-induced suppression, at supraoptimal concentration of Con A, to a lesser extent. Total numbers of histamine type 1 or type 2 receptors were not different for cells from atopic or normal dogs. The spontaneous suppression was significantly greater for the atopic dogs and this was not accounted for by the effect of non-specific dermatitis, increased macrophage-induced suppression or increased induction by mitogenic factors in the culture medium. Some possible mechanisms for these results are discussed, and the similarities to suppressor cell function in humans with atopic disease are noted.

Activated suppressor cell dysfunction in progressive multiple sclerosis.

Concanavalin A (Con A)-induced suppressor activity has previously been shown to be reduced in multiple sclerosis (MS) patients with active clinical disease. In this study, we demonstrate that OKT3, as well as Con A induced suppressor activity mediated by unfractionated peripheral blood mononuclear cells is reduced in patients with the progressive form of MS. By performing reconstitution experiments involving E+, T4+, or T8+ cells derived from either MS patients or controls, and normal allogeneic macrophages or E- cells, we sought to define the cellular basis for this suppressor defect. In both MS and control groups, E+ cells were required to obtain measurable levels of suppression. Suppressor levels induced by Con A-activated cultures containing E+ cells from MS patients were lower than those induced by those containing control donor E+ cells. Suppression mediated by T8+ cells from MS patients was also lower than for controls. In the control group, suppression mediated by T8+ cells exceeded that mediated by T4+ cells; such differences were not apparent in the MS group. These results suggest that although Con A-induced suppression can be mediated by a number of T and non-T cell subsets, the functional suppressor defect measured in the MS population does involve the T8+ cell subset.

Progressive multiple sclerosis: Abnormal immune functions in vitro and aberrant correlation with enumeration of lymphocyte subpopulations

In a series of 27 consecutive progressive multiple sclerosis (MS) patients under age 50 we have simultaneously measured 3 in vitro immune functions and 6 markers and compared their results to a group of 21 controls. We have confirmed a reduction of concanavalin A (Con A) -induced suppression and NK function contrasting with increased IgG secretion in response to pokeweed mitogen (PWM). Among 6 monoclonal antibody-recognized subpopulations (Leu 1, Leu 2, OKT8, Leu 3, Leu 7 and Leu 11) only Leu 2 + lymphocytes were statistically reduced. OKT8 + were slightly reduced, Leu 3 + were slightly increased. Discriminant analysis revealed that the 3 immune functions together with the results of OKT8 and Leu 3 enumeration were sufficient to appropriately classify most of the individuals. Only 3 MS and 4 controls were misclassified. Correlation analysis suggested disappearance of the doubly labelled OKT8/Leu 7 population in MS patients. In MS as opposed to controls Con A-induced suppression did not correlate with suppressor cell markers but correlated with NK cell markers suggesting that in MS this population mediates Con A-induced suppression. IgG secretion and Con A suppressor cell function were inversely correlated in MS patients but not in controls, suggesting that in chronic progressive multiple sclerosis a common abnormality underlies both increased response to PWM and decreased induction of suppression by Con A.

ACTIVATION OF CYTOTOXIC-SUPPRESSOR HLA-DR POSITIVE T LYMPHOCYTES IN CHRONIC HEPATITIS B VIRUS (HBV) INFECTION IN CHILDHOOD

Children with aCAH have impaired Concanavalin A(Con A) induced 'suppression of Pokeweed stimulated immunoglobulin synthesis. Since this system tests non-specific immunoglobulin production, we investigated suppression of in vitro production of antibody to Tetanus toxoid (TT), a T-dependent antigen, by lymphocytes from 11 children with aCAH and 14 age-matched healthy controls, all previously immunized. Both patients and controls had similar serum anti-TT levels (mean ± SEM 1.8 ± 0.85 lU/ml, 2.0 ± 0.86 IU/ml) and in vitro production of anti-TT in response to optimal dose of TT (0.005 IU/ml)(5.3 ± 0.88 × 10−3 IU/ml, 6.7 ± 0.94 × 10−3 IU/ml) as measured by ELISA. Suppressor function was induced by 24 hour incubation of lymphocytes with high dose TT (5 IU/ml) or with 20μg/ml Con A. Washed cells were then added to stimulated autologous lymphocytes. TT-induced suppression of anti-TT production was similar in patients (69.8 ± 4.2) and controls (72 ± 3.8%). In contrast, Con A-induced suppression of anti-TT was significantly lower in patients (15.7 ± 2.5%) than controls (46.7 ± 4.9% p<0.01 Rank Test). Our data indicate that antibody production to a T-cell-dependent antigen is under the control of at least two regulatory mechanisms, one antigen specific and one antigen non-specific, only the latter being defective in aCAH.

Reversal of Con A-induced suppression by a platelet-derived factor which binds to activated suppressor T cells

A platelet-derived factor found in serum as well as in platelet releasate prepared either with calcium ionophore or with thrombin was shown to reverse Con A-induced suppression of the plaque forming cell (PFC) response to sheep erythrocytes (SRBC) in vivo in (CB6)F 1 mice. In addition, as shown previously, lymphoma cell-induced suppression in SJL mice was similarly reversed. The factor could be injected prior to Con A on the day before SRBC injection, or on the same day as antigen with comparable results. It also enhanced PFC responses in the absence of Con A. Suppressor cell induction by Con A in vivo, as demonstrated by assay on PFC responses of normal spleen cells in vitro, was abrogated by simultaneous injection of the platelet factor. Cells from mouse spleen and lymph node, but not from thymus could absorb the factor from human serum at 4 °C. The phenotype of the relevant spleen cells was L3T4 −, Ly1 −, Ly2 +, Thyl +, Ly22 +, Qa1 +, Qa4 +, Qa5 +, and Ly6.IE +. These results suggest that this factor binds to activated peripheral T cells of the suppressor cell phenotype.

Effect of B-activin on human T suppressor cells

The authors studied the influence of B-activin on the effect of human concanavalin A (con A)-induced T suppressor cells and also on the process of induction of T suppressor cells by con A and stimulation of proliferative activity of lymphocytes by phytohemagglutinin (PHA). Con A-induced suppression and the effect of B-activin on it were studied in a system in which the test cell culture and the culture for induction of suppressors were prepared simultaneously. Peripheral blood was obtained from blood donors for the experiments and during the preparation of the experiments, /sup 3/H-thymidine was added. The results of investigation of the influence of B-activin on the effect of con A-induced suppressors and also on the process of their induction are given. It is concluded that B-activin blocks the effect of con A-induced human suppressor cells but does not affect their induction, and B-activin does not affect proliferative activity of lymphocytes induced by PHA.

Immune abnormalities associated with HLA-B8: Lymphocyte subsets and functional correlates

Mononuclear cell populations were enumerated in healthy young adults with or without the histocompatibility antigen HLA-B8. Mononuclear cell counts were lower in subjects with HLA-B8, as was reflected in lower absolute numbers of the cell subsets. When cell populations were compared as percentages of total mononuclear cells, subjects with HLA-B8 had significantly more B lymphocytes bearing IgM than did subjects without HLA-B8. The T4 T8 ratio was significantly increased in subjects with HLA-B8, due both to increases in OKT4 + cells and to decreases in OKT8 + cells. B-Lymphocyte function was compared in subjects with and without HLA-B8 by measuring pokeweed mitogen driven differentiation of B cells to IgM bearing blasts, and was significantly greater in subjects with HLA-B8. Subjects with HLA-B8 were also found to have decreased Con A-induced suppression. Alterations in lymphocyte subsets and lymphocyte functions may underlie the predisposition to autoimmunity associated with HLA-B8.

Deficient natural killer function in patients receiving immunosuppressive drugs: Analysis at the cellular level

Renal transplant recipients receiving low maintenance immunosuppression (azathioprine, 2 mg/kg/day, and prednisolone, 10 mg/day), tolerating their transplants well, and without viral infection disclose a profound depression of NK activity as assessed by 51Cr-release assay. By combining the analysis of the different steps of cytolysis with the agarose single-effector assays and the estimation of circulating large granular lymphocytes (LGL), the defect is shown to be due to a significant decrease of the number of NK cells capable of binding (% target-binding cells 2.0 ± 0.3 versus 5.7 ± 0.7 in normals, P < 0.001) and killing (% cytotoxic target-binding cells 12.4 ± 1.9 versus 22.0 ± 0.5 in normals, P < 0.001) of targets. There is also a significant reduction ( P < 0.001) of both percentages (1.0 ± 0.2 versus 3.3 ± 0.4 in normals) and absolute values (9.8 ± 2.4 versus 62.3 ± 8.0/μ1 in normals) of LGL. These observations indicate that depressed NK activity is due mostly to depletion of NK cells. Functional impairment of NK cells can also be involved. Lack of direct in vitro effects of drugs (6-mercaptopurine, hydrocortisone, and methylprednisolone) at concentrations likely to be reached in vivo during treatments and relative resistance of NK activity after in vivo steroid administration suggest that immunosuppressive drugs act at the precursor cell level or on regulatory mechanisms. Despite functional integrity of two suppressor cell systems of allogeneic NK activity (suppression induced by preculture of lymphocytes with Con A and suppressor granulocytes) in immuno-suppressed patients, tested on normal NK cells, NK cells of immunosuppressed patients did not disclose greater susceptibility to Con A-induced suppression. This analysis indicates that the depletion phenomenon is probably a major mechanism in NK depression of patients receiving immunosuppressive drugs.

Immunoregulation in juvenile chronic arthritis.

The presence of hyperimmunoglobulinaemia and antinuclear antibodies in patients with juvenile chronic arthritis (JCA) suggests a possible role for immunoregulatory abnormalities in the pathogenesis of the disease. This is further supported by the demonstration in the sera of such patients of an autoantibody active against a suppressor inducer T cell subset. To identify immunoregulatory defects in JCA, a method of measuring concanavalin A (Con A)-inducible lymphocyte suppression of IgG production in vitro has been established. Peripheral blood mononuclear cells were cultured in the presence of either medium alone, pokeweed mitogen (PWM), Con A, or PWM together with Con A. IgG present in culture supernates at 8 days was measured by a double-antibody radioimmunoassay. Spontaneous IgG synthesis by lymphocytes by both patients and child controls was found to be more than double that of lymphocytes from adult control subjects. However, lymphocytes of children (patients or controls) did not show stimulation of IgG production in the presence of PWM. Con A-induced suppression of spontaneous IgG synthesis was reduced compared to adult controls in both patients (p less than 0.02) and child controls (p less than 0.05). Con A-induced suppression of IgG synthesis in the presence of PWM was also reduced compared to adult controls in both patients (p less than 0.01) and child controls (p less than 0.01) but was also reduced in the patient group compared to the child controls (p less than 0.01). Thus, spontaneous IgG synthesis in children is increased compared to adults, and IgG-producing cells appear less subject to regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-specific T suppressor factor acts indirectly by arming a T acceptor cell which releases a nonspecific inhibitor of transfer of contact sensitivity and of DNA synthesis when exposed to antigen

Mononuclear cell populations were enumerated in healthy young adults with or without the histocompatibility antigen HLA-B8. Mononuclear cell counts were lower in subjects with HLA-B8, as was reflected in lower absolute numbers of the cell subsets. When cell populations were compared as percentages of total mononuclear cells, subjects with HLA-B8 had significantly more B lymphocytes bearing IgM than did subjects without HLA-B8. The T4T8 ratio was significantly increased in subjects with HLA-B8, due both to increases in OKT4 + cells and to decreases in OKT8 + cells. B-Lymphocyte function was compared in subjects with and without HLA-B8 by measuring pokeweed mitogen driven differentiation of B cells to IgM bearing blasts, and was significantly greater in subjects with HLA-B8. Subjects with HLA-B8 were also found to have decreased Con A-induced suppression. Alterations in lymphocyte subsets and lymphocyte functions may underlie the predisposition to autoimmunity associated with HLA-B8.

Special characteristics of cellular immune function in normal individuals of the HLA-DR3 type

Studies with a number of tests of in vitro cellular immune function have shown differences between DR3-positive normal individuals and those of other DR types. Increased Ig synthesis and decreased Con A-induced suppression were the most striking changes observed in this preliminary investigation. Further studies especially with additional suppressor cell assays appear waranted. The possibilities that such changes play a significant role in the development of diseases associated with the DR3 phenotype is discussed.

Cellular response to basic protein and T suppressor cells in multiple sclerosis.

Peripheral blood lymphocytes from patients with multiple sclerosis (MS) and two control groups, patients with neurologic diseases other than MS and healthy individuals, were examined for their cellular response to basic protein (BP), suppressor cell activity elicited by concanavalin A (ConA) and enumeration of T gamma cells. Lymphocytes from patients with active and chronic progressive MS showed the highest blastogenic stimulation in response to BP, the lowest ConA-induced suppression and the lowest absolute and relative number of T gamma cells. Lymphocytes from patients with nonactive or slowly progressive MS showed BP blastogenic stimulation similar to or slightly higher than that of the control groups. The ConA suppressor activity and the absolute and relative number of T gamma cells in the nonactive MS group were within normal ranges. The results indicate that although hypersensitivity to BP may be accompanied by deficient immunoregulatory activity, there is no pattern in the sequence of events. In addition, in some instances, changes in the immunoregulatory cells occurred with little or no effect on the cellular response to the neural antigen.

Histamine modulates in vitro IgG production by pokeweed mitogen-stimulated human mononuclear cells

The modulatory role of histamine was investigated in an in vitro model involving immunoglobulin production by human blood mononuclear cells. The addition of histamine in vitro had little effect on the spontaneous production of IgG (measured by double-antibody radioimmunoassay). However, the addition of histamine (10 −4–10 −9 M) to mononuclear cells stimulated with an optimun concentration of pokeweed mitogen (PWM) significantly suppressed IgG production in a dose-dependent fashion from 10 −4 to 10 −6, M (range 55-37% suppressor, respectively). The kinetics of histamine-induced suppression was investigated by adding histamine to mononuclear cells at the time of stimulation by PWM or up to 4 days later. Histamine only significantly suppressed PWM induced IgG synthesis if added up to 72 hr after the addition of PWM. In order to characterize the histamine-responsive suppressor cell in this system we employed a coculture technique and compared our findings to those of Con A-induced suppression. Mononuclear cells were either separated into E-rosette-positive (T-enriched) or E-rosettenegative (T-depleted) populations, irradiated, or treated with monoclonal antibodies plus complement; cells were then stimulated with histamine or Con A for 24 hr and cocultured with autologous E-rosette-negative populations that were then stimulated with PWM, and IgG production was measured. The histamine- and Con A-responsive suppressor cell was found within the T-enriched population, was radiation sensitive to 2000 and 3000 rad, respectively, and was identified by OKT8 antisera but not OKT4 antisera. Of particular interest, the addition of histamine to irradiated T cells and PWM-stimulated T-depleted populations did not result in suppression of IgG production, implying that B cells were not being inhibited directly by histamine. The nature of the histamine receptor present on the suppressor cell was investigated. The H 1 antagonist, diphenhydramine (10 −4, M), inhibited IgG production as effectively as histamine. The combinations of h 1 antagonist and histamine did not result in an additive effect. Cimetidine (10 −4, M), had no effect by itself on in vitro IgG production and the combination of cimetidine plus histamine in equimolar concentrations did not abrogate histamine-induced inhibition of IgG production. Studies employing the H 1 and H 2 agonists (10 −4 to 10 −6, M), 2-pyridylethylamine and Dimaprit, respectively, resulted in an equivalent suppression of IgG production. The H 1 and H 2 agonist-responsive suppressor cell was found in the T-enriched population and was sensitive to 3000 rad. These experiments imply that the histamine-reactive cell suppressing IgG synthesis may be activated through either its H 1 or H 2 receptor.

Effect of antilymphocyte antibody in systemic lupus erythematosus on in vitro Ig synthesis

The effect of systemic lupus erythematosus (SLE) serum on Con A-induced suppressor T cells was studied in in vitro Ig synthesis. Active SLE sera containing IgG antilymphocyte antibody (ALA) specific for Tγ markedly inhibited the suppressor T-cell activity, whereas either IgM ALA specific for Tγ or any Ig classes of ALA specific for Tγ(−) lymphocytes did not significantly affect the suppressor T-cell activity when compared with IgG Tγ-specific ALA. Other factors possibly present in SLE sera affecting suppressor T-cell activity were also examined in in vitro Ig synthesis assays. Aggregated human IgG used as a substitute for immune complexes inhibited Con A-induced suppression of IgG synthesis in a dose-dependent manner. However, their inhibitory rates were far less than those with active SLE sera containing IgG Tγ-specific ALA. Corticosteroids also strongly inhibited Con A-induced suppressor T-cell activity. In lupus serum the most inhibitory activity was present in IgG (7 S) fraction and removal of IgG from the sera by anti-human IgG-coated beads resulted in the loss of the inhibition against Con A-induced suppressor T-cell activity. These results suggested that the main inhibitory factors contained in active SLE sera for Con A-induced suppressor T-cell activity are the IgG type of Tγ-specific ALA and that other types of ALA may not contribute significantly. Circulating immune complexes and corticosteroids, if present in SLE sera, seemed to play a minor role in the inhibition of suppressor T-cell activity.

Concanavalin-A-induced suppressor lymphocytes in normal individuals.

Suppressor lymphocytes are now known to play an important role in the control of immune responses. It has been demonstrated that lymphocytes stimulated by the mitogen concanavalin A (Con A) have the ability to suppress the normal lymphocyte response to antigens. It has further been shown that this suppressive action is reduced when the suppressing lymphocytes are derived from patients with disorders (e.g. systemic lupus erythematosus) in which it has been suggested that suppressor cell function is abnormal. In this study we have examined several aspects of the Con A-induced suppression. The induction of suppression required viable cells, and both the induction and the action of the suppressor cells were radio-resistant. The induction of suppressor cells by Con A was independent of DNA synthesis but not of protein synthesis. The action of these suppressor cells was enhanced by the addition of prednisolone to the cultures. This latter observation is of interest in view of the action of steroids in diseases in which a defect of suppressor cells is suggested to be present and lends support to the importance of suppressor cells in the aetiology of these disorders.

Con A-induced suppressor cells in man II. Role of monocytes and their interaction with soluble inhibitory factors

Monocyte dependence of Con A-induced suppression was studied in co-cultures of normal human lymphocytes. Con-A-pretreated (25 µg/ml for 48 hours) peripheral blood mononuclear (MN) cells inhibited the 3H-thymidine uptake by fresh autologous or allogeneic lymphocytes stimulated with Con A. Monocyte-depleted lymphocytes pretreated with 25 µ/ml of Con A failed to exhibit the suppressor properties. Supernatants of MN cell activated with 25 µ/ml Con A for 72 hours inhibited the mitogenic response of fresh allogeneic cells when added in proportion 1 : 1 to the culture medium. No inhibition was observed when supernatants of monocyte-depleted, Con A activated cultures were tested. The short preincubation with suppressive supernatants rendered blood adherent mononuclear cells suppressive for 3H-thymidine incorporation by autologous MN cells stimulated with Con A. These studies indicate that monocytes are essential for induction of suppressor cells in Con A stimulated cultures. The suppressor cells produce a soluble inhibitory factor(s) which has the property of binding to the surface of fresh monocytes. Such monocytes become responsible for suppression of mitogenic response of autologous lymphocytes.

A comparative immunologic analysis of several murine strains with autoimmune manifestations

The genetic autoimmune disease (lupus-like) in mice of several strains (NZB, NZB × W, MRL 1 , MRL n , BXSB) has been analyzed comprehensively. Comparison of the histoimmunopathologic, serologic, and cellular characteristics of these mice reveals several pathogenic common denominators but no obvious etiologic factors in common. In all kinds of autoimmune mice studied, the lupus-like syndrome consists of a fatal immune complex glomerulonephritis, thymic atrophy, and lymphoid hyperplasia that varies in degree. The lymphoid hyperplasia is most prominent in MRL 1 mice and it is of T-cell origin. MRL 1 mice, in addition, may exhibit arteritis and arthritis. Serologically, all SLE mice have abnormally elevated serum Ig levels, antinuclear antibodies, anti-ds- and ssDNA antibodies, and anti-hapten antibodies. Some of the MRL 1 mice, in addition to the above antibodies, develop antibodies to Sm ( MRL 1 and MRL n ) and antiglobulins ( MRL 1 ). Natural thymocytotoxic antibodies and anti-erythrocyte antibodies are predominantly found in NZB and NZB × W mice. With advanced age and disease all lupus mice have depressed complement levels and circulating immune complexes. Some of these complexes in all lupus mice are composed of retroviral gp70-anti-gp70 antibodies, whereas MRL 1 mice, in addition, contain circulating IgG-IgG RF complexes. Characterizing the various recognized lymphoid cell surface markers, one notes that each strain of lupus mice has some variation from the normal distribution, but in no two of these strains are the abnormalities the same. The B cells of these mice seem advanced in maturity, whereas the developmental isotype diversity is normal in all of them. NZB and NZB × W mice are characterized by a nonspecific early B-cell hyperactivity but it is not known if this activity is responsible for their subsequent specific autoantibody production. The proliferating T cells of older MRL 1 mice seem to exert excessive helper activity on syngeneic B cells. Both antigen-specific and antigen-nonspecific Con A-induced suppression are within normal limits in all lupus mice. Although transfer studies have shown that the basic defect is associated with the lymphoid system, from our work and that of others it appears that the abnormalities in these mice are polygenic and different from one strain to another. Thus, murine lupus as a syndrome can be the result of many different abnormalities which eventuate in B-cell hyperactivity and involvement of a number of the available endogenous antigens in a systemic immune complex disease which is responsible for the “characteristic” clinical picture of systemic lupus erythematosus.

The in Vitro Suppression of Spontaneous Erythrocyte Autoimmune Responses with Lymphocytes Activated with Concanavalin A

Abstract When normal mouse spleen cells are cultured in vitro, large numbers of cells develop that produce antibody toward antigens found on bromelain-treated mouse erythrocytes (BrMRBC). The in vitro culture also generates T cells that mediate DTH toward these antigens. We have suggested that under in vivo conditions, suppressor T cells maintain these immune responses at a low level but that this suppression wanes when the cells are cultured in vitro. The present study examines the effect of concanavalin A (Con A) on the in vitro development of humoral and cell-mediated immunity to BrMRBC. Mitogenic concentrations of Con A prevented the development of both the PFC and TDTH responses toward BrMRBC. The Con A-induced suppression was due to the induction of suppressor T cells; thus the addition of Con A-activated cells to fresh spleen cell cultures prevented the development of both the PFC and TDTH response against BrMRBC.

Effect of Concanavalin A on Lymphocyte Interactions Involved in the Antibody Response to Type III Pneumococcal Polysaccharide

Abstract Concanavalin A (Con A) administered at the time of immunization induces suppression of the in vivo splenic plaque-forming cell (PFC) response to type III pneumococcal polysaccharide (SSS-III). As with low dose paralysis of the PFC response to SSS-III, Con A-induced suppression could not be demonstrated in congenitally athymic (nu/nu) mice and could be eliminated partially by treatment with anti-lymphocyte serum (ALS). The kinetics for Con A-induced suppression paralleled those for low dose paralysis of the antibody response to SSS-III. These findings support the view that Con A-induced suppression is produced in vivo by suppressor T cells and that this form of suppression shares with low dose paralysis a common pathway through which suppression is mediated.