Immunosuppressive effect of a trichothecene mycotoxin, Fusarenon-X in mice.

The in vitro treatment with Fusarenon-X, a mycotoxin produced by Fusarium nivale Fn 2B, depressed the mitogenic responses of mouse lymphocytes to the T-cell mitogens, phytohaemagglutinin (PHA) and concanavalin A (Con A), but to a lesser extent to B-cell mitogen, a bacterial lypopolysaccharide (LPS). The in vitro treatment of mice with Fusarenon-X also decreased the responsiveness of splenic lymphocytes to the T-cell mitogen, Con A. Administration of Fusarenon-X to BALB/c mice before immunization significantly reduced anti-DNP IgE and IgG1 responses, while the treatment of mice after immunization was less effective. The number of spleen cells of the treated mice was increased with a reduction of T lymphocytes and an increase of granulocytic elements. In vitro antibody responses of spleen cells from Fusarenon-X treated mice by pokeweed mitogen (PWM) or LPS were also suppressed. Reconstruction experiments using sIg positive and negative spleen cells from normal and Fusarenon-X treated mice showed that this inhibitory effect resided in the sIg negative cell population.     

Role for Macrophages and Thymus-Derived Lymphocytes in Cholera Toxin-Induced Immunosuppression

The exo-enterotoxin derived from Vibrio cholerae bacilli has marked immunomodulating activities, both in vivo and in vitro. In the present study, the mechanism whereby cholera toxin depresses the antibody-forming ability of murine splenocytes was investigated by in vitro reconstitution experiments. Spleen cells derived from mice treated with cholera toxin 2 days earlier were markedly deficient in their ability to respond to sheep erythrocytes upon challenge immunization in vitro. Addition of graded numbers of normal spleen cells to spleen cell cultures from toxin-treated mice partially restored the antibody response. Adherent splenocyte populations were even more effective in restoring antibody formation. Normal peritoneal exudate cells rich in macrophages were also capable of restoring the antibody-forming ability of toxin-pretreated splenocytes. Furthermore, thymus (T)-derived spleen cells from normal mice, as well as sheep erythrocyte "educated" T cells, were capable of restoring antibody formation to normal levels. The importance of T lymphocytes in restoring immune competence of spleen cell cultures from toxin-treated mice was shown by additional experiments in which T-depleted cell preparations were found to be ineffective in restoring antibody activity. These studies point to macrophages and T-derived lymphocytes as a major target for cholera toxin-induced immunosuppression.     

Lymphocyte activation: IV. The ultrastructural pattern of the response of mouse T and B cells to mitogenic stimulation in vitro

Thymocytes from cortisone-treated mice (`T' cells), `B' spleen cells (B lymphocytes from thymectomized, irradiated, marrow reconstituted mice) and normal spleen (T + B) cells were examined by electron microscopy after 60 hours stimulation by Concanavalin A (a T cell specific mitogen), endotoxin (B cell specific mitogen), and pokeweed mitogen (which stimulates both T and B cells). Stimulation of T cells by Con A or PWM induced the appearance of lymphoblasts (Type I) and only PWM or endotoxin stimulated B cells developed `plasmablast' features (dilated, vesicular rough endoplasmic reticulum; Type II). A few stimulated B cells also had lymphoblast morphology. Large cells from normal (T + B) spleen stimulated by PWM were heterogeneous consisting of 55–60 per cent plasmablasts and 40–45 per cent lymphoblasts. It was concluded that the ultrastructure of stimulated lymphocytes depended on whether T or B cells were stimulated and not primarily on the mitogen used. In general, the response evoked by mitogens paralleled at the ultrastructural level that induced by antigens. It was also found that multivesicular bodies and glycogen particles occurred predominantly in the cytoplasm of stimulated T cells (lymphoblasts).     

Enhancement of the in vitro antibody response in dietary protein restriction. Failure in the regulation of antibody synthesis.

We have studied the antibody response in vitro of spleen cells from C57BL/6 mice kept on a protein deficient (D) or a normal diet (N). Short or long term protein restriction initiated after weaning led to increased plaque forming cell (PFC) responses to sheep red blood cells (SRBC), TNP-ficoll and TNP lipopolysaccharide. The influence of dietary restriction on the suppression of the antibody response to SRBC was studied in mixed cultures of antigen sensitized and fresh, non-immune cells from either D or N donors. Addition of pre-sensitized D or N cells to non-immune N spleen cells in a 1:1000 ratio resulted in marked suppression of the PFC response whereas co-cultures of pre-sensitized cells and non-immune D spleen cells did not result in significant suppression. Similarly, non-immune T cells from DF mice exerted a lower suppressor effect than non-immune T cells from N mice. Either dietary restriction or low dose cyclophosphamide treatment of the donors of non-immune spleen cells determined a similar reduction in suppression. It is suggested that nutritional deficiency selectively depletes short-lived suppressor effector lymphocytes which are activated in the presence of antigen-stimulated inducer cells.     

Suppression of polyclonal immunoglobulin biosynthesis by a soluble factor: T-cell dependent and T-cell independent mitogens

When normal human spleen cells are pulsed with concanavalin A (Con A), a portion become suppressor cells which in co-culture can inhibit immunoglobulin synthesis by other normal spleen cells stimulated by pokeweed mitogen (PWM). One mechanism whereby these Con-A activated spleen cells suppress Ig synthesis appears to be by the secretion of a soluble suppressor factor(s) since supernatants of Con-A stimulated splenocytes also suppress the polyclonal synthesis of immunoglobulin by human spleen cells. In this study, we report that supernatants of Con-A activated spleen cells suppress the in vitro synthesis of IgG, IgM and IgA by human spleen cells cultured with PWM. Our results indicate that the soluble suppressor factor(s) blocks an early stage in the differentiation of B lymphocytes into plasma cells without affecting the synthesis and secretion of immunoglobulin by more mature lymphocytes which appear to be irreversibly committed toward the pathway of synthesizing immunoglobulin. In addition, we studied the ability of normal human spleen cells to synthesize polyclonal immunoglobulin when cultured with either the T-cell dependent PWM or T-cell independent mitogens lipopolysaccharide (LPS) and Nocardia. Our results demonstrate that normal human splenic mononuclear cells cultured with either Nocardia, LPS or PWM are significantly stimulated to synthesize polyclonal IgG, IgM and IgA. Furthermore, supernatants of Con-A activated human spleen cells suppressed the polyclonal synthesis of these three antibody classes by human spleen cells responding to either T-cell dependent or independent mitogens.     

Abnormal behavior of gamma-committed B lymphocytes probed by a lymphocyte blastogenesis inhibitory factor in autoimmune MRL mice

Recently, we have characterized a lymphocyte blastogenesis inhibitory factor (LBIF) which was purified from the culture supernatant of a human histiocytic lymphoma U-937 (Sugimura, K. et al., Eur. J. Immunol. 1989. 19: 1357). In this study, we investigated the effect of LBIF on the antibody production of autoimmune MRL mice in vitro. We demonstrated here that (a) LBIF inhibited the IgM, IgG and IgA antibody responses of lipopolysaccharide (LPS)-stimulated spleen cells of normal BALB/c mice, (b) in the case of old autoimmune MRL/Mp-lpr/lpr (MRL/l) and MRL/Mp-(+)/+ mice, however, LBIF inhibited IgM and IgA but not IgG responses of LPS-stimulated spleen cells, (c) the antibody production of all IgG subclasses, IgG3, IgG1, IgG2b and IgG2a, was not sensitive to LBIF inhibitory activity in these autoimmune mice, (d) in young MRL mice (3-5-week-old MRL/l), which were phenotypically normal, LPS-induced antibody production of all isotypes (IgM, IgG and IgA) was strongly inhibited by LBIF as shown in normal BALB/c mice and (e) in the case of 7-week-old MRL/l the insensitivity to LBIF was concomitant with the appearance of gamma + B lymphocytes. Thus, by employing LBIF as a probe, this study showed a correlation between the pathogenesis of MRL autoimmune disease and the lack of LBIF sensitivity of hyperactive B lymphocytes and suggested that the intrinsic abnormality of autoimmune MRL B lymphocytes might be confined to gamma- but not mu- or alpha-committed B cells.     

Deficiency of CD26 results in a change of cytokine and immunoglobulin secretion after stimulation by pokeweed mitogen

To investigate the role of CD26 in the immune system, CD26 gene knockout mice with C57BL/6 background were used to study the immune response after stimulation with PWM. CD26(-/-) mice display an apparently normal phenotype. However, in their spleen lymphocyte population the percentage of CD4(+) T cells is lower, and that of NK cells is higher, than that in CD26(+/+) mice. In their peripheral blood, CD26(-/-) mice present a conspicuously decreased proportion of CD4(+) NKT lymphocytes. In vitro, the PWM-stimulated IL-4 production was decreased by 60-80% in the supernatants of spleen lymphocytes of CD26(-/-) mice compared to that of CD26(+/+) mice, whereas levels of IL-10 and IFN-gamma were increased. No significant differences were found in the production of IL-2, IL-5, IL-6 and IL-13 between knockout and wild-type mice. After immunization of mice with PWM in vivo, serum levels of total IgG, IgG1, IgG2a and IgE were markedly lower in CD26(-/-) mice than those in CD26(+/+) mice, while no difference was found in IgM production. Further analysis of cytokine levels in vivo revealed a reduced IL-4, IL-2 and delayed IFN-gamma production in sera of CD26(-/-) mice upon immunization with PWM. These results indicate that CD26 contributes to the regulation of development, maturation and migration of CD4(+) T, NK and NKT cells, cytokine secretion, T cell-dependent antibody production and immunoglobulin isotype switching of B cells.     

Levamisole enhances immune response by affecting the activation and maturation of human monocyte-derived dendritic cells

The primary aim of this study was to evaluate the role of natural killer (NK) cells on antigen-specific adaptive immune responses. After analysing the mechanism of impaired adaptive immune responses of NK-depleted mice, an immune interventional approach was developed to restore adaptive immunity in NK-depleted mice. NK cells were depleted from mice by administration of anti-asialo GM1 antibody (100 mul/mouse), twice, at an interval of 48 h. Hepatitis B surface antigen (HBsAg) was administered intraperitoneally to normal C57BL/6 mice (control mice) and NK-depleted mice. The levels of antibody to HBsAg (anti-HBs) in the sera and HBsAg-specific lymphocytes in the spleen were assessed. The functions of T lymphocytes, B lymphocytes and dendritic cells (DCs) were evaluated in vitro. HBsAg-pulsed DCs were prepared by culturing spleen DCs with HBsAg for 48 h and administered once to NK-depleted mice. The levels of anti-HBs in the sera and HBsAg-specific lymphocytes were significantly lower in NK-depleted mice compared with control mice (P < 0.05). The functions of T and B lymphocytes were similar between control mice and NK-depleted mice. However, the functions of spleen DC and liver DC were significantly lower in NK-depleted mice compared with control mice (P < 0.05). Administration of HBsAg-pulsed DCs, but not HBsAg, induced HBsAg-specific humoral and cellular immune responses in NK-depleted mice. Our study suggests that cross-talk between NK cells and DCs regulates the magnitude of adaptive immunity. In addition, antigen-pulsed immunogenic DCs represent potent immune modulator even if subjects with diminished innate immunity.     

Functional Analysis of Pokeweed Mitogen-Dependent Cell Interactions in Murine Spleen Cells

The nature of lymphocyte responses on addition of pokeweed mitogen (PWM) to normal murine spleen cells was studied in low cell density cultures. PWM, over a wide range of concentrations, stimulated proliferation in a set of cells roughly 10-fold smaller than the lymphocyte populations responding to either concanavalin A or lipopolysaccharide. PWM also induced a relatively small number of B lymphocytes in these cultures to mature to Ig-secreting plaque-forming cells (PFC). Proliferative and PFC responses were completely abrogated by T-cell removal from normal spleen cell cultures. Moreover, cell mixture and irradiation experiments demonstrated that B lymphocytes do not proliferate in response to PWM, even in the presence of an excess of normal T cells, suggesting that PFC development results from terminal maturation without proliferation. Finally, parallel titrations of cloned helper cells, normal splenic T cells or T-cell blasts induced by PWM showed that the poor B-lymphocyte responses in normal spleen cell cultures is due to the very low frequency of competent helper cells in these populations. PWM, however, was competent to activate and expand this set of helper lymphocytes in primary cultures.     

Immunoregulation in experimental filariasis. IV. Induction of non-specific suppression following in vitro exposure of spleen cells from infected jirds to Brugia pahangi antigen.

Studies with inbred jirds chronically infected (greater than 5 months) with Brugia pahangi have demonstrated splenic suppressor cells which modulate in vitro responsiveness to mitogens and parasite antigens. The stimuli which induce suppression were characterized by analysing the effect of activated cells from inbred normal or B. pahangi-infected jirds on the PHA and PWM responsiveness of cultures on normal cells. Regulatory cells were stimulated in vitro with concanavalin A (Con A; 5 micrograms/ml) or an extract of adult B. pahangi (20 micrograms/ml) for 72 hr and irradiated (1500 rads) prior to cocultivation with normal cells. Addition of Con A-activated normal spleen cells to normal cells produced moderate suppression of PHA and enhancement of PWM responsiveness. However, Con A-stimulated spleen cells from infected animals consistently suppressed both the PHA and PWM responsiveness of normal cells by 80-90%. Spleen cells from chronically infected jirds were also induced by B. pahangi antigen to suppress both the PHA and PWM responsiveness of normal lymphocytes. In contrast, spleen cells from animals 3-15 weeks after infection and lymph node cells from all time points were capable of suppressing only PWM responses when stimulated by antigen. Normal spleen cells were not induced by B. pahangi antigens to exhibit immunoregulatory activity. The suppression mediated by antigen-induced spleen cells from chronically infected jirds was partially or totally alleviated by removal of non-specific suppressor cells which are plastic adherent and cyclophosphamide-sensitive, or by removal of antigen-specific suppressor cells which bear receptors for histamine. the results suggest the involvement of regulatory cell circuits in experimental filarial infections.     

Influenza virus depresses the PFC response of mice by affecting T-cell function

Five influenza virus strains of type A and one strain of type B were used to elicit suppressive effect on the formation of antibody producing cells in response to sheep red blood cells (SRBC) both in vivo and in vitro. Not only live virus but also the formalin inactivated one exerted immunosuppression (IS). Although intranasal infection only could cause disease in mice, it exerted no IS which, in contrast, occurred after intraperitoneal or intravenous injection of the virus. In nude mice these effects were not seen, but they could be elicited when transferred with normal T cells. The antibody response to T cell independent antigen such as DNP was normal. Thus, it was proved that influenza virus induced T cell dependent immunodeficiency. However, T cell enriched population from infected mice when cultured with normal spleen cells could not suppress their PFC response in vitro. This suggested that suppressor T cells were not required for the immunodeficiency caused by influenza virus.     

Suppressor lymphocytes induced by epicutaneous sensitization of UV-irradiated mice control multiple immunological pathways.

The purpose of this study was to determine whether the formation of hapten-specific suppressor T lymphocytes induced by the epicutaneous sensitization of UV-irradiated mice could suppress other hapten-specific immune responses in addition to contact hypersensitivity (CHS). Suppressor cells were induced by applying trinitrochlorobenzene (TNCB) to the unexposed skin of mice irradiated several days earlier with 40 kJ/m2 UVB (280-320 nm) radiation. Previous work demonstrated that the spleens of such animals contain Lyt-1+, 2-T lymphocytes which prevent the induction of CHS to TNCB when transferred to normal mice, and inhibit proliferation of normal lymphocytes in vitro to TNP-modified syngeneic cells. These studies show that addition of T lymphocytes from UV-irradiated, TNCB-sensitized mice to cultures of normal lymphocytes and TNP-modified syngeneic cells inhibited the generation of TNP-specific cytotoxic T lymphocytes (CTL). The inhibition was dose-dependent and occurred only when the suppressor cells were present during the first 24 hr of culture. The suppressor cells had no effect on the activity of preformed CTL. In addition, injection of the suppressor lymphocytes into mice at the time of i.v. injection of TNP-modified sheep red blood cells (TNP-SRBC) reduced the number of direct plaque-forming cells against TNP, but had no effect on the production of antibody against SRBC. Cells that inhibited anti-TNP antibody formation were Thy-1+, Lyt-1+, 2-. These results indicate that hapten-specific suppressor cells from UV-irradiated mice prevent the activation of several different hapten-specific immunological pathways.     

Adjuvant and mitogenic properties of a supernatant fraction of sonically treated Myobacterium bovis (BCG).

A water-soluble, oil-free supernatant fraction of sonically treated BCG (BCG-SS) was shown to be an immunological adjuvant and a mitogen. When BCG-SS and sheep erythrocytes (SRBC) were injected intravenously into mice, the plaque-forming cell (PFC) response was 10 times greater than that induced by injection of SRBC alone. Circulating antibody responses to SRBC and to bovine serum albumin were also enhanced by BCG-SS. The in vitro enhancement of PFC and circulating antibody responses did not require mineral oil or exogenous lipids. In vitro PFC responses by normal mouse spleen cells were also greatly increased in the presence of BCG-SS. Anti-theta serum-treated spleen cells from mice that had been lethally irradiated and reconstituted with normal bone marrow cells also gave a higher PFC response to SRBC in the presence of BCG-SS. This suggests that BCG-SS can stimulate B lymphocytes to develop an immune response when T lymphocytes are severely depleted or absent. BCG-SS also stimulated the uptake of 125IUdR by normal spleen cell cultures, indicating that it is a mitogen.     

Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model

Mammalian pregnancy is thought to be a state of immunological tolerance. The mechanisms underlying this phenomenon are still poorly understood. Here, we determined whether an inappropriate function of T regulatory (Treg) cells is involved in the pathogenesis of spontaneous abortion. We evaluated spleen and decidual lymphocytes from CBA/J mice undergoing immunological abortion (DBA/2J-mated) or having normal pregnancy (BALB/c-mated) on day 14 of gestation for ex vivo cytokine production after PMA or paternal antigen (alloantigen) stimulation. Treg activity was characterized by quantifying CD4(+)CD25(+) cells, foxp3 expression, and interleukin-10 secretion. Decidual lymphocytes from abortion CBA/J mice contained a significantly higher frequency of interferon-gamma-producing T cells specific for paternal antigens compared to those from normal pregnancy (7.8% versus 2.7%, P < 0.05). Compared to virgin CBA/J females, normal pregnant mice showed strongly elevated numbers of CD4(+)CD25(+) and interleukin-10(+) Treg cells in the thymus whereas significantly lower frequencies of Treg cells were observed in abortion mice. Very interestingly, CD4(+)CD25(+) Treg cells from normal pregnant and nonpregnant CBA/J mice could inhibit both proliferation and interferon-gamma secretion of lymphocytes from abortion mice in vitro whereas in vivo prevention of fetal rejection could only be achieved after adoptive transfer of Treg cells from normal pregnant mice. Our data suggest that pregnancy-induced Treg cells play a vital role in maternal tolerance to the allogeneic fetus.     

Inhibition of IgE production of mice by non-specific suppressor T cells.

SWR adult normal splenic T lymphocytes injected into irradiated syngeneic mice along with immune spleen cells can suppress IgE formation by the immune cells. Spleen cells from 1- or 3-week-old mice, however, are not effective in abrogating IgE synthesis. The T lymphocytes which are induced to become suppressors for IgE are hydrocortisone-resistant and anti-thymocyte serum-sensitive. Normal SJL mice, a poor reagin-producing strain, do not appear to have more suppressor cells or cells which are more easily stimulated to become suppressor cells than a good reagin-producing strain (SWR).     

Partial characterization of a T cell-derived factor that suppresses the initiation of the humoral immune response in vitro.

Specific anamnestic stimulation of spleen cells from mice immunized 7 days earlier with horse erythrocytes (HRBC) generated the release of a soluble factor that was capable of suppressing the initiation of the in vitro primary gammaM immune response to sheep red blood cells (SRBC), as well as to the immunogen that elicited its formation. Moreover, the suppressive macromolecule (mol. wt yields to 34,000), derived from antigen-activated, HRBC-primed T lymphocytes (but not B cells), inhibited the secondary gammaM and gammaG anti-SRBC plaque-forming cell responses of SRBC-primed spleen cells. The active material was resistant to treatment with DNase and RNase, but was inactivated by protease (10 microgram/ml, 30 min) or exposure to mild heat (56 degrees, 30 min). The antibody initiation suppressor factor (AISF) was concentrated and partially purified by gel filtration, followed by poly-acrylamide gel electrophoresis.     

Antibody production and DNA synthesis of human lymphocyte subpopulations induced by PPD tuberculin.

Purified protein derivative (PPD) of tuberculin was found to induce antibody secretion and DNA synthesis in human lymphocytes from blood, spleen, tonsil and lymph node. Antibody secretion was measured as plaque-forming cells (PFC) against fluorescein isothiocyanate (FITC) coupled sheep red blood cells (SRBC) in a haemolysis-in-gel assay. Peak antibody secretion by 100 micrograms/ml of PPD was usually seen on day 6 for blood lymphocytes, and varied from day 3 to day 6 for spleen cells. Peak DNA synthesis for blood lymphocytes stimulated by various concentrations of PPD ranged from day 4 to day 7. The highest number of PFC in tonsil and spleen cells was induced by PPD compared to Staphylococcus aureus bacteria Cowan 1, lipopolysaccharide (LPS) and pokeweed mitogen (PWM). Antibody secretion by PPD was not affected when phagocytic cells were removed by iron treatment. PPD stimulated a higher DNA synthesis in unseparated lymphocytes or mixtures of T and B cells than in enriched T or B cell suspensions. PPD did not induce PFC in B cells enriched by the removal of sheep erythrocyte rosette-forming cells (E-RFC). However, more PFC were stimulated by PPD in enriched E-RFC compared to unseparated lymphocytes, which may indicate that most of the FITC-SRBC reactive B cells also form rosettes with SRBC.     

Appearance of non-specific suppressor T cells during in vitro culture.

It was found that when normal mouse spleen cells were cultured for 4 days they were capable of non-specifically suppressing the in vitro antibody response of non-precultured spleen. The suppression was mediated by a subpopulation of viable, non-adherent, T lymphocytes with the surface phenotype Ly-1+, Ly-2- and Ia-. Furthermore, it appeared that the suppressor cells were responding to foetal calf serum antigens present in the tissue culture medium and were subsequently inactivating either B lymphocytes or accessory cells required for antibody formation, which had passively absorbed these antigens.     

The effect of aging on IgD receptor expression by T cells and its functional implications

Summary: Exposure to oligomeric or aggregated (a), but not to mono-merle (m), IgD causes a rapid (within 1 h) upregulation of IgD-R expression on CD4⁺ T cells from young, but not from aged, mice and on both CD4⁺ and CD8⁺ T cells from all young and from =65% of aged humans. In normal young (but not in IgD^−/-) mice, this increase in IgD-R expression is associated with a marked increase in primary and secondary antibody responses, transferable to both aged and young mice with T cells from aIgD pretreated donors. In both species, immunization causes a rise in the IgDR⁺ expression in vivo in the young. In mice, mIgD abolishes both the Induction of IgD-R expression and augmentation of immune responses, suggesting that interaction between IgD-R⁺ T and IgD⁺ B cells is needed. In aged humans, the ability of peripheral blood lymphocytes to exhibit IgD-R expression in response to aIgD in vitro or to influenza vaccine in vivo is strongly correlated to the individual's ability to produce antibody. In T cells from aged mice, but not from aged IgD-non-responder humans, IgD-R are able to come to the cell surface if an additional signal has been supplied, such as by (ionomycin/thapsigargin + aIgD). Agents which induce IgD-R and augmentation of antibody production in aged and young mice include phosphatidylcholine and dehydroepiandrosterone sulfate. The immunoaugmenting effect of pretreatment with these agents appears Indeed due to IgD-R⁺ T cells, because it is abolished by mIgD.     

Induction of suppressor cells by sodium periodate: the opposite expression of periodate-induced lymphocyte activation in spleen cells of normal and nude mice.

Normal mouse spleen cells treated with sodium periodate for 10 min at 4 degrees are stimulated to undergo blastogenesis and to incorporate thymidine. In contrast, periodate treatment does not stimulate DNA synthesis in nude mice spleen cells. The effect of such treatment on the antibody response in vitro induced by sheep red blood cells (SRBC) and by trinitrophenyl polyacrylamide (TNP-PAA), a T-independent antigen has been evaluated. Periodic-induced proliferation is accompanied by a marked inhibition of the immune response to both of these antigens in normal mouse spleen cells. Mild oxidation of nude cells with periodate markedly enhances their anti-TNP response elicited by TNP-PAA. The data suggest that periodate-induced immune suppression is associated with T lymphocytes. Furthermore, periodate-treated cells are capable of suppressing the in vitro antibody response of untreated normal cells.