PFC Response Research Articles

Primary antibody responses to thymus-independent antigens in the lungs and hilar lymph nodes of mice

B lymphocytes from the pulmonary lymphoid tissues were stimulated with a variety of thymus-independent (TI) antigens by intratracheal (i.t.) immunization. Immune responses in the lungs and hilar lymph nodes (HLN), which are part of the localized lymphoid tissue, as well as in the spleen, the systemic lymphoid organ, were studied. Thus, primary i.t. immunization of mice with the TI-1 antigen trinitrophenyl-lipopolysaccharide (TNP-LPS) elicited both antigen-specific and polyclonal plaque-forming cell responses from HLN, lung, and splenic B lymphocytes. These responses appeared as early as 3 days after immunization and declined by day 7. Similar immunization with another TI-1 antigen, TNP-Brucella abortus, resulted in anti-TNP responses in both pulmonary and systemic lymphoid tissues, although the kinetics of the antibody response were different than those to TNP-LPS. Interestingly an i.t. immunization with a TI-2 antigen, TNP-Ficoll, failed to induce an anti-TNP PFC response from HLN and lung B cells, although there was good antibody formation from splenic B cells. Antibody response to TNP-Ficoll was restored in pulmonary tissues when mice were immunized with TNP-Ficoll mixed with unconjugated B. abortus. In conclusion, our results indicate that TI-1 and TI-2 antigens differ in their ability to induce antibody responses in the pulmonary lymphoid tissues. The inability of TNP-Ficoll to elicit an antibody response in pulmonary lymphoid tissues has significance in the development of vaccines containing bacterial polysaccharides.

A NOVEL SULPHATE CONJUGATE OF CYCLOSPORINE OCCURRING IN HIGH CONCENTRATIONS IN VIVO

A novel, water-soluble metabolite of cyclosporine, a sulphate conjugate, present in high concentrations in human bile and plasma was evaluated for its immunosuppressive properties. The direct binding of the conjugate to surface molecules on lymphocytes was studied. The effect of the metabolite was tested in several in vitro systems, including MLR and mitogen-induced proliferation, Il-2 production, generation of CTL, and expression of surface antigens on lymphocytes after stimulation with mitogens. In vivo, the drugs were tested for suppression of the PFC response against SRBC. The results show an inhibitory effect of the conjugate in the generation of CTL and to some extent in the production of Il-2 but not in any of the other systems. The concentrations needed to achieve these effects exceeded those of CsA with a factor of 500-5000.

Copper Deficiency during Perinatal Development: Effects on the Immune Response of Mice

Dietary copper (Cu) was restricted in Swiss albino mice during five discrete intervals over a 9-wk period of perinatal development: gestation only (G), lactation only (L), 3 wk postlactation (PL), 1 wk after birth through postlactation (2/3L + PL), and lactation plus postlactation (L + PL). Biochemical and immunological status of mice in copper-deficient (-Cu) treatment groups in models G and L did not differ from that of copper-adequate (+Cu) controls. Signs of severe copper deficiency, such as low liver copper levels, and significant reductions in activity of plasma ceruloplasmin and splenocyte Cu-Zn superoxide dismutase were most evident in 6-wk-old mice from two groups, -Cu 2/3L + PL and -Cu L + PL. Mice in these groups were anemic and had small thymuses and enlarged spleens compared to controls receiving +Cu treatment. The -Cu mice demonstrated impaired antibody (plaque-forming cells, PFC) response to sheep erythrocytes, and the attenuation was proportional to copper deficiency, as judged by liver copper levels. Total plasma IgM levels were not greatly altered by -Cu treatment except in model L + PL. Total IgG levels were markedly reduced in this group and in the -Cu 2/3L + PL group. The PFC response of mice in the -Cu PL group was normal even though signs of copper deficiency were evident; however, the PFC response was reduced when -Cu treatment was extended to 5 wk and was reversible by switching to +Cu treatment. Splenocyte reactivity to B- and T-cell mitogens was not greatly different between groups. Incorporation of thymidine into DNA in the absence of mitogen was higher in -Cu mice. It is evident that severity of copper deficiency is related to degree of impaired immunity. Furthermore, severity of copper deficiency is dependent on duration and time of initiation of dietary copper restriction.

Characterization of the immunodeficiency of RIIS/J [corrected] mice. I. Association with the CD5 (LY-1) [corrected] B cell lineage.

RIIIS/J mice produce low antibody responses to several polysaccharide Ag of bacterial origin. They have low levels of serum IgM and IgG3 and high levels of serum IgG2a and IgG2b. Low serum IgM and IgG3 have been attributed to a low frequency of CD5 (Ly-1) B cells, which play an important role in the production of natural antibodies. Indeed, RIIIS/J mice have a low frequency of CD5 (Ly-1)+, IgM bright+, Ly-5 (B220)dull+ (i.e., CD5 (Ly-1) B) cells in their peritoneum. RIIIS/J mice treated with LPS produce a low anti-bromelain-treated mouse RBC splenic plaque-forming cell response and a normal anti-mouse transferrin splenic PFC response. Those data are compatible with the fact that CD5 (Ly-1) B cells contain the precursors of B lymphocytes secreting anti-bromelain-treated mouse RBC antibody. However, they have a higher frequency of IgM bright+, Mac-1+ cells in their peritoneum. These cells represent the CD5 (Ly-1) "sister population" of CD5 (Ly-1) B cells described by others. This suggests that characteristics usually associated with the CD5 (Ly-1) lineage are applicable only to the CD5 (Ly-1)+ Mac-1+ IgM+ population, but not the related CD5 (Ly-1)- Mac-1+ IgM+ population. RIIIS/J mice should thus prove a valuable model to study the CD5 (Ly-1) B cell lineage.

Preferential expansion of Ly-1 B and CD4− CD8− T cells in the polyclonal lymphocyte responses to murine T.cruzi infection

Acute murine infection with T. cruzi results in polyclonal lymphocyte responses manifested by blast transformation of a large fraction of B, CD4+, and CD8+ cells. We describe here the finding of significant increases in the splenic representation of minor populations, Ly-1 + B cells and CD4-CD8- T cells. These lymphocyte populations might play an important role in the host response, as shown by T. cruzi infection of hosts that had been lethally irradiated and reconstituted with autologous bone marrow. Under these conditions, the splenic polyclonal PFC responses are nearly abrogated, and not restored by the transfer of syngeneic peritoneal cells which, however, reconstitute T15 idiotype production in the same hosts. Control levels of PFC responses, however, are reconstituted by transfer of syngeneic splenic T cells. Since bone marrow-reconstituted animals contain normal numbers of CD4+ and CD8+ T cells which are actually activated by infection, these results suggest the participation of other T cell populations in the host response to infection, as also suggested by the marked increases in T cell receptor gamma and delta messages detected in the spleen of infected animals. The implications of these findings in immunopathology of Chagas' disease are discussed.

Participation of IL-4 in the formation of IgD-binding factors by antigen-primed mouse spleen cells.

BALB/c mouse spleen cells primed with either keyhole limpet hemocyanin or DNP-keyhole limpet hemocyanin formed not only IgG-binding factors (BF) and IgE-BF but also IgD-BF upon antigenic stimulation. Analysis of cellular mechanisms involved in the formation of Ig-BF by antigenic stimulation revealed that Ag-primed Th cells released lymphokines upon antigenic stimulation, and that the lymphokine(s) in turn stimulates unprimed T cells to form Ig-BF. Normal unprimed lymphocytes formed IgD-BF upon incubation with culture supernatants of Ag-stimulated spleen cells. The formation of IgD-BF induced by the culture supernatant was prevented by anti-IL-4 mAb (11B11). It was also found that 0.3 to 10 U/ml mouse rIL-4, but none of the rIL-1, IL-2, and IFN-gamma, induced normal T cells to form IgD-BF. Indeed, both IL-2 and IFN-gamma inhibited IL-4 to induce the formation of IgD-BF. In contrast, 10 to 50 U/ml of IFN-gamma induced the formation of IgE-BF, and 50 to 200 U/ml IFN-gamma induced the formation of IgG-BF. However, none of the other lymphokines tested, i.e., IL-1, IL-2, and IL-4, induced the formation of either IgE-BF or IgG-BF. The IgD-BF formed by antigenic stimulation of keyhole limpet hemocyanin-primed spleen cells and those formed by stimulation of normal lymphocytes with 1 to 2 U/ml IL-4 enhanced both IgM and IgG1 plaque-forming cell responses of SRBC-primed spleen cells to homologous Ag. In contrast, 1 to 2 U/ml of IL-4, which could induce the formation of IgD-BF, failed to affect the PFC responses. It appears that the formation of IgD-BF may be involved in the effects of IL-4 to enhance the antibody response.

CD4+ T cells are required for development of a murine retrovirus-induced immunodeficiency syndrome (MAIDS).

Mice depleted in vivo of CD4+ Th cells by treatment with mAb GK1.5 were found to be resistant to the lymphoproliferative/immunodeficiency disease (MAIDS) induced in intact mice by infection with the mixture of LP-BM5 murine leukemia viruses. Depleted mice did not develop lymphadenopathy or splenomegaly, had normal serum IgM levels, normal CTL responses to alloantigens, and were able to generate PFC responses to Th-independent antigens even though frequencies of virus-producing spleen cells were comparable in depleted and intact mice. Depletion of CD4+ Th cells after infection resulted in a reversal of many abnormalities exhibited by infected controls; spleen weights, serum IgM levels, and allogeneic CTL responses of treated mice were comparable to those of uninfected controls. These results demonstrate that dysfunction of CD4+ Th cells is central to the induction and progression of both T and B cell abnormalities in MAIDS.

Studies on suppressor factors produced by T-cell hybridomas: I. Characterization of antigen-specific suppressor factors

Antigen-specific and antigen-nonspecific suppressor T cells were generated when spleen cells prepared from C57BL/6J (H-2 b) were incubated with trinitrophenylated polyacrylamide beads (TNP-PAA) in vitro. T hybridomas were prepared by fusion of spleen cells cultured with TNP-PAA for 4 days and the thymoma cell line BW5147. More than 100 hybridomas were generated, and 15 of them suppressed the anti-TNP PFC response of fresh spleen cells cultured with TNP-PAA. The suppression was antigen specific with three of these five hybridoma supernatants tested. Hybridomas that caused antigen-specific suppression secrete factors which bring about suppression of the anti-TNP PFC response by spleen cells cultured with TNP-PAA. These hybridoma supernatants which cause antigen-specific suppression typically depressed the anti-TNP PFC response by 60% while depressing anti-SRBC PFC response by only 10%. The antigen-specific suppressor factors were bound to a TNP-BGG column but not to a BGG column. The suppressor factors, purified by affinity chromatography on a TNP-BGG column, were bound to anti-I-J b antibody.

Immunoregulatory aberrations in patients with polyarticular juvenile rheumatoid arthritis

The presence of hypergammaglobulinemia and various circulating autoantibodies in children with polyarticular juvenile rheumatoid arthritis (JRA) implies an immunoregulatory disorder. We report here experiments planned to elucidate the underlying cellular aberrations in this disease. Twelve children with polyarticular JRA were studied. Percentages of Leu-1, Leu-2, and Leu 3 T cells were comparable to those of normal individuals. Immunofluorescent double staining studies demonstrated elevated numbers of activated (DR +) T cells of both Leu-2 and Leu-3 phenotype. B cells characterized both phenotypically (Leu-12) and functionally (as spontaneous plaque-forming cells, PFC) were elevated. In vitro PFC responses to pokeweed mitogen (PWM) and Epstein-Barr virus (EBV) were diminished. The levels of concanavalin A-induced suppressor cells of the PWM-stimulated PFC responses were comparable to control values. In contrast, the EBV-associated suppressor T cells were significantly impaired in both EBV-seropositive and EBV-seronegative patients. These studies indicate that peripheral blood B-cell activity is abnormal in polyarticular JRA. Defective T-cell responses in vitro suggest that this may be due to disruption of normal regulatory circuits between B and T cells and may contribute to the pathogenesis of this disease.

Regulation of in vivo immunological reactions by monoclonal antibody against lymphocyte activation antigen.

In vivo effects of a monoclonal antibody that recognizes rat lymphocyte activation antigen were studied. Spleen cells obtained from sheep red blood cell (SRBC)-immunized rats developed strong PFC response against SRBC. However, the 5C6-F4 treatment resulted in the inhibition of subsequent development of PFC response. The suppression of PFC response was due to the inhibition of generation of helper T cells, but not due to the preferential induction of suppressor cells. In addition, 5C6-F4 antibody was also found to inhibit the clinical expression of collagen-induced rat arthritis and the synovial inflammation in collagen-induced arthritis rats. Furthermore, the in vivo generation of cytotoxic cells against syngeneic tumor cells was also inhibited by 5C6-F4 antibody. The in vivo administration of 5C6-F4 antibody did not cause any pathological changes in brain, lung, liver, kidney, spleen, thymus, and lymph nodes.

Anti-α 1–6 epitope, specificity of a T-cell hybrid-secreted factor: Affinity- and ion-exchange chromatographic separation

We have studied the specificity of the products of a “T-cell” hybridoma, Th 1, a fusion product of AKR thymoma BW 5147 with spleen cells from Dx-hyperimmunized mice, which has been shown to affect the anti-Dx but also the anti-SRC response from culture supernatants and ascitic fluids. The anti-Dx-affecting material was separated from unspecific effector molecules by Sephadex affinity chromatography combined with HPLC DEAE chromatography and gel filtration. The activities of fractions were tested for their effects on anti-Dx, anti-SRC, and anti-SSS-III IgM responses. We show that the anti-Dx response-affecting material binds to Sephadex. Its Ig contamination can be reduced by two DEAE chromatographies at pH 6 and 8.1. At pH 8.1 it starts eluting with 0.13 M NaCl, but is still contaminated with materials that affect the anti-SRC and to a smaller extent the anti-SSS-III response. On gel filtration it localizes in the area of 100-40 kDa. The effects of the active material on anti-Dx IgM varied from suppression to enhancement. The details of that effect are largely unknown but three other findings further confirm the Dx specificity of Th 1 products. The growth of Th 1 in mice induces the production of anti-Dx IgA, detectable in their sera with ELISA. The priming of mice with Th 1 products affects the magnitudes of anti-Dx IgM PFC responses to the subsequent immunization with Dx with or without the product. The binding to Dx of material from in vivo active fractions can be verified in the ELISA with an antiserum produced against Th 1.

An antigen-specific helper T cell hybridoma produces an antigen-specific suppressor inducer molecule with identical antigenic fine specificity. Implications for the antigen recognition and function of helper and suppressor inducer T cells.

We have previously described a T cell hybridoma, A.1.1, that responds to specific Ag (P18, a synthetic polypeptide of defined sequence) in the context of I-Ad by producing lymphokines. Herein we report that this cell also releases, into culture supernatants and ascites fluid, an Ag-specific activity that functions in the induction of suppression of anti-SRBC PFC responses. This suppressive activity requires a) Ag-non-specific accessory molecules from a T suppressor inducer factor, b) Ly-2+ T cells in the assay cultures, and c) the specific Ag (P18) conjugated to the SRBC in the assay cultures. The specificity of the A.1.1-derived activity was demonstrated by the absence of suppression in cultures containing SRBC, BSA-SRBC, or conalbumin-SRBC rather than P18-SRBC. Further, the A.1.1-derived activity bound to, and could be eluted from, P18 but not conalbumin. Using a panel of synthetic variant peptides, we have mapped the critical residues in P18 required for Ag/I-Ad induced activation of A.1.1. These peptides were tested for their ability to act as targets for the A.1.1-derived suppressive activity when conjugated to SRBC and added to assay cultures. All peptides capable of stimulating the A.1.1 T cells to release lymphokines were similarly effective in the suppressor assay. Thus, the recognition of Ag by the T cells and by the T cell-derived activity appeared to be identical. The A.1.1-derived molecule was found to be capable of inducing L3T4- T cells to act as suppressor T cells following culture. These suppressor cells were active in inhibiting anti-SRBC responses in the absence of P18 and bore the Ly-2 surface marker. Thus, it is likely that the function of this Ag-specific molecule is to induce Ly-2+ suppressor T cells and thereby cause the inhibition of the response. This function is distinct from that normally associated with helper T cells and may shed new light on the possible relationship between the cell surface T cell receptor for Ag and Ag-specific T suppressor inducer molecules.

Primary and secondary IgG are equally efficient immunosuppressors in relation to antigen binding capacity

Secondary, hyperimmune IgG antibodies can suppress the humoral immune response against the relevant antigen. Whether IgG antibodies derived from a primary antigen response also have this capacity is not clear, although the role of primary IgG is of great interest in a physiological situation. In this study we compared the in vivo immunosuppressive potential of primary and secondary IgG anti-SRBC (sheep erythrocytes) on the primary anti-SRBC PFC response in CBA/Ca mice. Both primary and secondary IgG antibodies are potent immunosuppressors causing more than 99% specific suppression. Preparations of primary and secondary IgG antibodies which, measured by an ELISA method, were shown to bind to SRBC to the same extent, also had very similar immunosuppressive potency. This emphasizes the strong correlation between the antigen binding and the immunosuppressive capacities of IgG antibodies.

ｉｎ ｖｉｔｒｏ自己抗体産生に及ぼす免疫調節剤および免疫抑制剤の影響

Anti-DNA antibodies were released in the culture supernatant of spleen cells from BALB/c and autoimmune NZB/W F1 mice by the addition of LPS. The authors investigated the effect of several immunomodulators and immunosuppressants on the in vitro production of anti-DNA antibody. It was demonstrated that the anti-DNA antibody production in both mouse strain was not reduced by levamisole (LMS), bucillamine (SA96), and lobenzarit disodium (CCA), all which augmented the in vitro anti-SRBC PFC response. On the contrary, mizoribine, salazosulfapyridine (SASP), and platonin (NK-19) inhibited both anti-DNA antibody production and anti-SRBC PFC response. Mizoribine and SASP reduced the viability of cultured splenocytes, but NK-19 didn't. The results shows that every anti-rheumatic drug tested had a diffent action on the anti-DNA antibody production, suggesting the importance of further studies for their clinical application.

The suppressive effect of histamine on anti-DNP antibody production in mice.

To clarify the effect of histamine on antibody production, histamine was injected intravenously into DNP-KLH immunized C3H/HeN female mice. The number of anti-DNP plaque-forming splenic cells decreased in immunized and histamine-injected mice. Decreased PFC responses similarly occurred in recipient mice into which Lyt-2.1 T cells obtained from histamine-injected mice were transferred before immunization. The effect of histamine is not due to inhibition on plaque formation. The results indicated that histamine induced the augmentation of suppressor T cell (Ts) function and caused the decrease of antibody production in histamine-injected mice. The maximum activity of Ts in recipient mice was obtained from mice injected with histamine 3 days before the cell transfer. The suppressive activity of histamine was not antigen specific because Ts was induced in histamine-injected, nonimmunized mice. The treatment of histamine type 2 (H2) agonist showed decreased PFC responses in the mouse as well as histamine did. When mice were treated with an H2 antagonist followed by histamine, antibody production was not reduced. The above results indicated that histamine seemed to regulate antibody production through H2 receptors on lymphocyte membranes.

The effect of sublethal endrin exposure on rainbow trout, Salmo gairdneri Richardson. II. The effect of altering serum cortisol concentrations on the immune response

The effect of altering serum cortisol concentrations on the immune response was elucidated in endrin‐ and non‐endrin‐exposed rainbow trout, Salmo gairdneri. Fish were immunized with 10 μg of Yersinia ruckeri O‐antigen following 30 days of treatment. The migration inhibition factor assay (MIF), plaque‐forming cell assay (PFC) and serum agglutination titres (SAG) were performed 2, 14 and 30 days post‐antigen inoculation. Endrin exposure was continued subsequent to antigen inoculation. Control fish were fed 20 and 35 mg kg−1 body weight day−1 of cortisol and metyrapone, respectively. Endrin‐exposed fish received 35 mg kg−1 body weight day−1 of metyrapone in their diet. Control fish receiving cortisol had significantly reduced MIF, PFC and SAG responses. The MIF response was completely restored in endrin‐exposed fish receiving dietary metyrapone. The PFC response and SAG titres were partially restored, 61 and 69% respectively, in endrin‐exposed fish receiving metyrapone. The results indicate that elevated serum cortisol concentration obtained in endrin‐exposed fish has a central role in repression of the immune response.

Age restriction in antigen-specific immunosuppression.

Age-related alterations of antigen-specific T cell-mediated suppression have been examined in the 4-hydroxy-3-nitrophenyl acetyl (NP) system. Inducer suppressor T cells (Tsi) were activated in mice at the age of 3 mo (young) or 18 mo (old) by i.v. injection of NP-conjugated syngeneic spleen cells (SC). Spleen cells from the NP-SC-injected mice were subcultured in vitro with spleen cells from normal young or old mice to generate transducer suppressor T cells (Tst). Four days later subcultured cells were added to responder cell cultures 1 day before the PFC assays to trigger effector suppressor T cells (Tse). Responder cell cultures, containing NP-conjugated horse red blood cells (HRBC) and spleen cells from HRBC-primed young or old mice, were assayed on day 4 for anti-NP and anti-HRBC PFC. Suppression was found to be antigen specific and age restricted. NP-specific suppressor cells are easily induced in subculture if the Tsi and Tst cell populations are both derived from young or old mice. Conversely, if Tsi cells from young or old mice are subcultured with Tst cells from mice of a different age, suppression of the anti-NP PFC response is hardly observed. Age restriction was also found to operate in the interactions between subcultured and responder cell populations, indicating that age-matching is required for effective triggering of Tse cells by Tst cells. These results altogether suggest that aging may affect the recognition repertoire expressed in suppressor T cell subsets. Moreover, the finding that suppression is less efficient when exerted on responder spleen cells from old than from young mice provides an explanation for the increased frequency of autoimmune disorders in aging.

A role for histamine type II (H-2) receptor binding in production of the lymphokine, soluble immune response suppressor (SIRS).

Soluble immune response suppressor (SIRS) is an immunosuppressive protein produced by human and murine suppressor cells activated by a variety of agents. Because histamine has been reported to activate suppressor cells, the possibility that it also induced SIRS production was investigated. Human lymphocytes treated with 10(-4) M histamine for less than 1 hr released a suppressive substance into culture supernatants that was physically, functionally and antigenically similar to human SIRS. Cimetidine and ranitidine, structurally distinct histamine type II (H-2) receptor antagonists, prevented histamine-induced SIRS production. In further experiments, suppression of human polyclonal IgM PFC responses by Con A and interferons, substances that activate the SIRS pathway, was inhibited by H-2 receptor antagonists. Activation of lymphocytes to produce SIRS by Con A or interferons was blocked by cimetidine or ranitidine. These data demonstrate that production of SIRS is induced by histamine, and raise the possibility that H-2 receptor binding may play a role in the SIRS pathway.

Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen-presenting cells.

Purified, recombinant-derived murine granulocyte-monocyte colony-stimulating factor was found to enhance the primary in vitro immune response to SRBC by murine spleen cells. In determining the mechanism of this augmentation, it was found that only splenic adherent cells and neither resting nor activated T cells nor B cells expressed specific receptors for GM-CSF. When splenic adherent cells were pulsed briefly with GM-CSF before addition to macrophage-depleted cultures, they reconstituted the PFC response to a significantly greater degree than did control macrophages. Splenic adherent cells incubated overnight with SRBC plus GM-CSF were also more efficient antigen-presenting cells than splenic adherent cells incubated with antigen alone. The mechanism of this enhanced antigen presentation was found to be due to a GM-CSF-dependent increase in the level of IL 1 secretion and Ia antigen expression. Consistent with these data was the finding that GM-CSF augmented IL 2 production by splenic T cells in response to suboptimal concentrations of Con A. Finally, the day 5 in vivo antibody response (as measured by serum titers) of mice immunized with a low dose of SRBC was enhanced by two daily inoculations of GM-CSF. Thus, the role that GM-CSF plays in augmenting immune responses may not be solely accounted for by its ability to cause the proliferation or differentiation of macrophages, but more than likely includes its ability to enhance the function of antigen-presenting macrophages.

Influence of plasmodium chabaudi adami on the isotypic distribution of the antibody response of mice to sheep erythrocytes

The influence of an infection with P. chabaudi adami on the isotypic distribution of the in vivo antibody response to SRBC was investigated. Previous experiments suggested that the IgGI isotype was poorly represented in the antibody response to plasmodial antigens and in the non-specific B cell response which accompanies an infection with P. chabaudi. The experiments described here indicated that although the magnitude of the total primary or secondary in vivo PFC response to SRBC was relatively unaffected by infection, the SRBCspecific IgG 1 PFC response was depressed. Maximum depression of the IgG 1 component of the response was observed when the priming dose of SRBC was administered at the same time as or after infection with P. chabaudi organisms. Coincident with the depression in the IgG 1 response in infected mice was a corresponding increase in the SRBC-specific IgM response. The IgG 1 depression was not a consequence of different kinetics of the generation of an IgG 1 response, since at all times measured, the IgG 1-PFC response was lower. In addition, the depressed IgG 1 responses occurred only during a viable infection and could not be induced by inoculation of large amounts of irradiated erythrocytic stages of the parasite. These data suggest therefore, that there is a selective depression of IgG 1 antibodies (but not those of other isotypes) regardless of antigenic specificity as a result of infection of C57BL/6 mice with P. chabaudi adami.