Effects of Anti-T Cell (Theta) and Anti-B Cell (Beta) Serum on the Immune Response in Mice

Heterologous anti-B cell (anti-beta) serum was prepared in rabbits against the spleen from neonatally thymectomized mice. The anti-beta serum, after absorption with thymus, is cytotoxic for bone marrow, bone marrow-derived cells, fetal liver and peritoneal lymphocytes. The cytotoxicity to the B cell can be absorbed out with bone marrow.

The cytotoxic effects of anti-beta serum on spleen and lymph node cells is compared to that of anti-theta serum. The data suggest that spleen has relatively more B than T cells, while lymph node has relatively more theta-positive cells.

To test the effect of anti-beta and anti-theta serum on the functional activity of lymphoid cells, C57 spleen or thymus was pre-incubated with the antiserum, in the presence of complement, and tested in vivo for graft-vs-host activity or transfer of an adoptive immune response to SRBC.

Treatment with anti-beta serum does not decrease the graft-vs-host activity of thymus or spleen cells. Anti-theta serum does decrease the graft-vs-host activity of both thymus and spleen cells.

Neither anti-beta serum nor anti-theta serum affect the phagocytic activity of peritoneal macrophages.

Both anti-beta serum and anti-theta serum decrease the transfer of an adoptive primary and secondary immune response to SRBC. A combination of anti-theta and anti-beta treated spleen can transfer adoptive immunity. Thymus and bone marrow can reconstitute the immunocompetence of anti-theta or anti-beta treated spleen respectively.

The results suggest that T cells alone can mount a graft-vs-host reaction and that this activity is not affected by anti-beta serum. The transfer of a humoral antibody response, on the other hand, requires functionally active T- and B-cells. This holds true for a primary as well as secondary immune response. Our anti-beta serum does not appear to have any anti-macrophage activity.     

Effects of Various Anti-T Cell Receptor Antibodies on the Development of Type II Collagen-Induced Arthritis in Mice

Recent genetic studies of David and coworkers suggest that subsets of T cells utilizing specific Vβ TcR genes may play important roles in the susceptibility to collagen-induced arthritis (CIA). Hence, in vivo depletion of such T cell subsets may significantly affect the development of CIA. To address this possibility, we first examined the effects of in vivo treatments with various monoclonal antibodies (mAbs) that are specific for particular TcR Vβ families on the induction of CIA. Results presented in this study demonstrated that treatments with either anti-Vβ6, anti-Vβ8 or anti-Vβ11 did not suppress the development of arthritis in collagen-immunized mice. While combined treatments with these Vβ specific mAbs which resulted in the in vivo elimination of Vβ6⁺, Vβ8⁺ and Vβ11⁺ T cells were not very effective in preventing the onset of CIA, the severity of the arthritic disease was somewhat reduced in animals that had received the triad of anti-Vβ mAbs. By contrast, depletion of T cells expressing the αβ receptors by in vivo treatments with a pan anti-αβ mAb significantly decreased the incidence of CIA. Therefore, although an effect on the development of CIA was achieved by in vivo treatments with a mAb that detects all αβ⁺ T cells, the elimination of only a few subsets of T cells which included the Vβ6⁺, Vβ8⁺, and Vβ11⁺ cells did not profoundly alter the incidence of CIA. Finally, these results suggest that other T cell subsets expressing different TcR V genes may also contribute to the disease process of CIA.     

Effects of Carbon Dust Inhalation on the Cell-Mediated Immune Response in Mice

The effects of carbon dust inhalation on the bone marrow-derived (B) and thymus-derived (T) lymphocyte populations of spleen and mediastinal lymph node (MLN) cultures were examined. The concanavalin A (Con A)-responsive cell population (T cells) in the spleen was found to be depressed after 7 days of pre-exposure to carbon dust. However, this effect was transient, and after 14, 21, and 28 days of pre-exposure to carbon dust, the Con A-responsive cells exhibited a 30 to 40% enhancement over control group responses. Conversely, Con A-responsive cells in the pooled MLN cultures exhibited depression, ranging from 22 to 33% below control group values, after 7, 14, and 28 days of pre-exposure to carbon dust. The lipopolysaccharide (LPS)-responsive cell population (B cells) in the spleens of carbon-exposed mice was found not to differ significantly from control group values after all times of pre-exposure. LPS-responsive cells in the MLN cultures exhibited enhancement, ranging from 49 to 74% above control values, after 14, 21, and 28 days of pre-exposure to carbon dust. The ability of carbon spleen cell cultures from carbon-exposed mice to undergo antigen induced blast transformation after sensitization with Mycobacterium tuberculosis H37Ra was also determined. Mice exposed to carbon dust inhalation 2 weeks before and 3 weeks after aerosol or subcutaneous immunization exhibited significantly enhanced ratios of transformation upon culture of their spleen lymphocytes with purified protein derivative of tuberculin.     

Bacterial Immunostimulant (Broncho-Vaxom) Versus Levamisole on the Humoral Immune Response in Mice

A comparative study on the enhancement of humoral immune response in mice after oral treatment with levamisole or a lyophilized bacterial lysate (Broncho-Vaxom) is presented. The latter proves to be more effective at therapeutic doses than levamisole on the induction of immunoglobulin formation and particularly that of IgA in secretions.     

Bacterial Immunostimulant (Broncho-Vaxom) Versus Levamisole on the Humoral Immune Response in Mice

Abstract

A comparative study on the enhancement of humoral immune response in mice after oral treatment with levamisole or a lyophilized bacterial lysate (Broncho-Vaxom) is presented. The latter proves to be more effective at therapeutic doses than levamisole on the induction of immunoglobulin formation and particularly that of IgA in secretions.     

Specific Features of the Immune Response in Old Recipient Mice to Cell Therapy

Implantation of somatic cells from autopsy specimens (15-18 weeks gestation) had a modulatory effect on immunogenesis in old mice. Activation of the immune system in recipient animals after administration of somatic cells reflects a multistage influence of test preparation. The observed changes were reversible. A progressive decrease in activation of the immune system in recipient mice was not accompanied by the development of pathological changes. Repeated implantation was required to maintain these processes. Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 1, pp. 48-51, 2009     

Modulation of Exploratory Behavior in Mice during Activation of Cell Immune Response

We revealed a modulating effect of cell immune response on exploratory activity of (CBA°C57Bl/6)F1 mice depending on their initial behavioral profile. The formation of BCG-induced delayed-type hypersensitivity was accompanied by stimulation of the exploratory behavior in animals with initially low or intermediate activity, but did not change this parameter in behaviorally active mice.     

Effects of Monoclonal Anti-T Cell Antibodies on Rat Cardiac Allografts

Monoclonal antibodies reactive with different T lymphocyte antigens were administered to rats receiving heart allografts. Ox 19 antibodies (directed to the rat Ly 1 equivalent) and Ox 8 antibodies (directed to the rat CD8 equivalent) both prolonged graft survival, whereas W3/25 (anti-CD4), Ox 6 (anti-Ia), and W3/13 (anti-pan T) antibodies did not affect graft rejection. Immunohistological studies were carried out on spleen and graft specimens in order to analyse further the mechanisms behind the prolongation of graft survival. The observed almost complete absence of Ox 8-reactive cells in the spleen after treatment with Ox 8 antibodies corroborates earlier observations that injection of moderate amounts of Ox 8 antibodies leads to complete elimination of suppressor/cytotoxic T cells from peripheral lymphoid organs and blood. The present data on graft survival therefore both support the notion that suppressor/cytotoxic T cells are involved in graft rejection, and suggest that these cells are not the only ones involved. An unexpected and as yet unexplained finding was that Ox 8-reactive molecules were found in large numbers on various inflammatory cells as well as on certain myocytes in the grafted hearts that had experienced a prolonged graft survival due to treatment with Ox 8 or Ox 19 antibodies.     

Effect of Biophytum sensitivum on Cell-Mediated Immune Response in Mice

Effect of Biophytum sensitivum on cell-mediated immune response was studied in normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of Biophytum sensitivum significantly enhanced the proliferation of splenocytes, thymocytes and bone marrow cells by stimulating the mitogenic potential of various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A), Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell activity was enhanced significantly by Biophytum sensitivum in both the normal (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day 5), and it was found to be earlier than tumor bearing control animals (maximum of 13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was also enhanced significantly in both Biophytum treated normal (35% cell lysis on day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11). An early antibody dependent complement mediated cytotoxicity (ACC) was also observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor bearing animals (26.4% cell lysis, on day 15). Results of our present study suggest the immunomodulatory property of Biophytum sensitivum.     

Effect of Biophytum sensitivum on Cell-Mediated Immune Response in Mice

Effect of Biophytum sensitivum on cell-mediated immune response was studied in normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of Biophytum sensitivum significantly enhanced the proliferation of splenocytes, thymocytes and bone marrow cells by stimulating the mitogenic potential of various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A), Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell activity was enhanced significantly by Biophytum sensitivum in both the normal (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day 5), and it was found to be earlier than tumor bearing control animals (maximum of 13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was also enhanced significantly in both Biophytum treated normal (35% cell lysis on day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11). An early antibody dependent complement mediated cytotoxicity (ACC) was also observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor bearing animals (26.4% cell lysis, on day 15). Results of our present study suggest the immunomodulatory property of Biophytum sensitivum.     

Effect of Thyroxine on the Immune Response of Mice in Vivo and in Vitro

The effect of thyroxine on the immune response of BALB/c mice to sheep erythrocytes was investigated. In mice rendered hypertiyroid by subcutaneous injections of T4 the primary immune response to an injection of SRBC in vivo did not show a consistent increase in splenic anti-SRBC plaque-forming cells. However, the total number of splenic cells in T4-treated mice was generally decreased, and thus, the number of PFC per 10⁶ splenic cells in T4-treated mice was higher than those of saline and buffer controls. In in-vitro primary response to SRBC PFC per culture (3×10⁷ splenic cells) increased significantly in T₄-injected animals as compared with controls. The calculated PFC per spleen also increased significantly. The addition of T₄ to normal splenic cell cultures enhanced the primary immune response to SRBC in vitro. The optimum concentration of T₄ was found to be 10^-8 M. These results indicate a direct enhancing effect of T₄ on the immune response of lymphoid cells. This enhancing effect, however, may be attenuated in vivo by the alteration of the number and/or composition of lymphoid cells brought about directly or indirectly by injections of exogenous thyroxine.     

Modulatory Effect of the Pesticide Captan on the Immune Response in Rats and Mice

The effect of short-term oral administration of captan, [N-(trirnethylthio)-4-cyclohexene-1,2-carboximidel on the immune response was studied in rats and mice. Animals were fed a diet with or without 0.3 % (w/w) of captan for 7, 14, 21 and 42 days. The SRBC-antibody formation was depressed by about 70 % in both species after 14 days of treatment. A release of inhibition occurred in mice at day 42. In a parallel manner, the lymphoblastic stimulation of splenic cells by PHA and by LPS was studied in captan-treated mice and their controls. The stimulation by PHA of splenic cells that were mainly T cells was clearly inhibited (45 %) by day 14 of captan ingestion. Thereafter, the inhibition was only partially released until day 42. B cells, stimulated by LPS, presented a decrease in stimulation in captan-treated mice, during the first week of diet (20 %). Then an important increase in the stimulation of these cells occurred at day 21 (85 %) followed by a return to the normal value at day 42. These results pointed out a clear depressive effect of captan-diet on the immune response of the animals. The inhibition of SRBC-antibody formation during the first stage of the treatment may be correlated to the inhibitory effect of captan on T cells, which were cooperative with B cells for the expression of SRBC-antibody synthesis. These effects were obtained at a level of captan which was considerably lower than the toxic dose.     

Modulatory Effect of the Pesticide Captan on the Immune Response in Rats and Mice

Abstract

The effect of short-term oral administration of captan, [N-(trirnethylthio)-4-cyclohexene-1,2-carboximidel on the immune response was studied in rats and mice. Animals were fed a diet with or without 0.3 % (w/w) of captan for 7, 14, 21 and 42 days. The SRBC-antibody formation was depressed by about 70 % in both species after 14 days of treatment. A release of inhibition occurred in mice at day 42. In a parallel manner, the lymphoblastic stimulation of splenic cells by PHA and by LPS was studied in captan-treated mice and their controls. The stimulation by PHA of splenic cells that were mainly T cells was clearly inhibited (45 %) by day 14 of captan ingestion. Thereafter, the inhibition was only partially released until day 42. B cells, stimulated by LPS, presented a decrease in stimulation in captan-treated mice, during the first week of diet (20 %). Then an important increase in the stimulation of these cells occurred at day 21 (85 %) followed by a return to the normal value at day 42. These results pointed out a clear depressive effect of captan-diet on the immune response of the animals. The inhibition of SRBC-antibody formation during the first stage of the treatment may be correlated to the inhibitory effect of captan on T cells, which were cooperative with B cells for the expression of SRBC-antibody synthesis. These effects were obtained at a level of captan which was considerably lower than the toxic dose.     

Serum and Nasal Secretion Immune Response in Meningococcal Disease

Nasal antibodies to meningococcal organisms were demonstrable by the indirect fluorescent-antibody test in three patients. Serogroup cross-reactions were usual.     

The Primary Immune Response in Mice III. Retention of Sheep Red Blood Cell Immunogens by the Spleen and Liver

The antibody-inducing activities of foreign red blood cell immunogens sequestered in the spleens and livers of mice injected with sheep erythrocytes were evaluated during the early periods of the immune response. Estimates of immunogenicity, obtained from the magnitudes of anti-sheep red blood cell hemolysin responses evoked in sensitized recipient mice by subcellular tissue fractions prepared from these phagocytic organs, showed that the liver and spleen differ greatly in their handling of this particulate antigen. The liver, functioning primarily as a scavenger organ, destroys completely the immunogenicity of the heterologous erythrocytes in 12 hr. In contrast, the spleen handles foreign erythrocyte immunogens in at least two different ways: approximately 90% of the initially sequestered activity is rapidly destroyed by the spleen in 6 hr, but the remaining activity, associated chiefly with a tissue fraction possessing the sedimentation properties of "light mitochondria," is retained at a significant level for 3 days, and then progressively decreases to a low level until the 7th day. A correlation of the observed changes in the properties of the immunogenic tissue fraction with known cellular events in the spleen stimulated by antigens indicates that the retention of the degradable erythrocyte immunogen is essential for stimulating and maintaining immune reactions in this antibody-producing organ.     

Pleiotropic Effects of Cell Wall Amidase LytA on Streptococcus pneumoniae Sensitivity to the Host Immune Response

The complement system is a key component of the host immune response for the recognition and clearance of Streptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to S. pneumoniae, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the lytA ply double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia.     

Cryptococcus neoformans CAP10 Gene Regulates the Immune Response in Mice

The capsule associated protein 10 gene (CAP10) is indispensable to the formation of the polysaccharide capsule, and is closely associated with Cryptococcus (C.) neoformans virulence. In this study, we designed the shRNA expression plasmid to interfere with the synthesis of CAP10 gene. We infected mice with yeast cells in the respiratory tract, and monitored the development of infections in lung tissues. Results showed that the cap10-shRNA group may alleviate pathological lesions in pulmonary C. neoformans infection, and a lower degree of inflammatory cells was observed in the cap10-shRNA group. Moreover, the fungal burden was significantly lower in the cap10-shRNA group, indicating that the clearance towards C. neoformans was somehow affected. Down-regulation of CAP10 was beneficial to the balance of Th1/Th2 and Th17/Treg ratios. Collectively, our results showed that the expression of CAP10 was associated with an antifungal immune response in mice, suggesting that CAP10 regulates the inflammatory response. Therefore, we expect that the CAP10 gene will become a new molecular therapeutic target in cryptococcosis treatment.     

Effect of Boar Seminal Immunosuppressive Component on Humoral Immune Response in Mice

PROBLEM: The effect of seminal immunosuppressive component (ISF) on the primary and secondary antibody response, induced by soluble and/or corpuscular antigens, was evaluated in the sera obtained at different intervals before and after immunizations. The duration of the immune suppression induced by ISF treatment within the primary and secondary immunizations was also determined. METHOD OF STUDY: The ability of the seminal immunosuppressive component to suppress the primary and secondary antibody response was evaluated by enzyme-linked immunoadsorbent assay (ELISA) in the sera of mice treated in vivo with the immunosuppressor before and after immunization with antigens. Likewise, the duration of the immune suppression induced by the seminal immunosuppressor administered before the primary and secondary immunizations was tested by ELISA with antisera to keyhole limpets hemocyanin. RESULTS: Intravenous and rectal deposition of ISF led to a suppression of the primary and secondary antibody response to soluble and corpuscular antigens. The most effective suppression of the immune response was achieved in mice treated with immunosuppressor 3 days before the immunization with antigens. Also the secondary antibody response to the challenging antigen was significantly suppressed by ISF. The production of immunoglobulin G (IgG), IgM, and IgA to keyhole limpets hemocyanin was depressed for a relatively long period in mice treated with the immunosuppressor. The results indicated that the preexposure is needed for maximal immunosuppression of the primary antibody production. The treatment with ISF led to a prolonged immunosuppression but not to permanent tolerance to the challenging antigen. CONCLUSIONS: The in vivo deposition of semen may compromise some aspects of the immune system and may be an important factor in the development of viral and bacterial infections. The suppression of humoral immune response suggests potential uses of seminal immunosuppressor for the animal model study in the therapy of antibody-mediated diseases.