P. Sayles - Academia.edu (original) (raw)
Papers by P. Sayles
Journal of immunology (Baltimore, Md. : 1950), 1988
Inbred and H-2 congenic mouse strains were tested for their ability to resist infections with the... more Inbred and H-2 congenic mouse strains were tested for their ability to resist infections with the non-lethal 17X or with the lethal YM isolates of Plasmodium yoelii. DBA/2 and B10.D2 mice, which best resisted infections with non-lethal P. yoelii, were exquisitely susceptible to infection with lethal isolates of this malaria species. In contrast, B6 and B10 mice, which were susceptible to infection with non-lethal P. yoelii, were resistant to infection with the lethal isolates. This reversal of host response phenotype was influenced by H-2 genes, as evidenced by the divergent responses of the H-2 congenic strains B10 and B10.D2. However, a survey of mouse strains sharing common H-2 genes, but expressing different genetic backgrounds, demonstrated that genes outside the H-2 complex also influence the outcome of P. yoelii infections. By enumerating the numbers of P. yoelii-specific antibody-secreting cells in the spleens of infected mice, it was demonstrated that B6 mice, although susc...
The American Journal of Tropical Medicine and Hygiene, 1991
The role of the spleen in resistance to infections with nonlethal Plasmodium yoelii 17x is depend... more The role of the spleen in resistance to infections with nonlethal Plasmodium yoelii 17x is dependent upon the genotype of the host. Thus, DBA/2 (D2) mice infected with P. yoelii 17x were not adversely affected by removal of the spleen, while splenectomized C57BL/6 (B6) or Balb/c mice failed to resolve their infections and eventually died. The levels of parasitemia were lower in splenectomized mice compared to intact controls; however, splenectomized mice became as anemic as did spleen-intact controls. Splenectomy resulted in the appearance of large aggregates of mononuclear cells in the livers of infected mice and also altered the liver/body weight ratios. These results indicate that D2 mice have a spleen-independent mechanism of clearing parasites which is lacking in B6 and Balb/c mice.
Toxoplasma gondii infection in mice. CR3-dependent resistance to acute
The Journal of Immunology, 2007
Infection and Immunity, 1977
The immunodepressive effect of Toxoplasma gondii infection in mice was studied, using sheep eryth... more The immunodepressive effect of Toxoplasma gondii infection in mice was studied, using sheep erythrocytes (SRBC) as the testing antigen and serum hemagglutinins, hemolysins, and both direct and indirect splenic plaque-forming cells (PFC) to SRBC as assays. In the primary antibody response, immunoglobulin M (IgM), hemagglutinins, and hemolysins and both IgM- and IgG-secreting PFC were depressed in animals immunized after infection. Maximum immunodepression occurred during the first 3 weeks of Toxoplasma infection. When the secondary antibody response was studied, results varied. Mice immunized with SRBC after being infected with T. gondii had a depression in both IgM and IgG PFC. Mice immunized with SRBC before being infected with T. gondii and then given a challenge dose of SRBC had a delay, but no an actual depression, in IgG hemagglutinins and hemolysins and IgG-secreting PFC. These studies show that the immunodepression associated with Toxoplasma infection is complicated, and they...
Immunology, 1996
Although gamma delta T cells are found in increased numbers in the spleens of humans and mice inf... more Although gamma delta T cells are found in increased numbers in the spleens of humans and mice infected with malaria, it is not known if these cells are necessary components of an effective immune response. The surface phenotype of spleen cells obtained from mice infected with avirulent Plasmodium chabaudi adami or virulent Plasmodium chabaudi chabaudi were examined using anti-delta or anti-alpha beta T-cell-specific reagents and flow cytometry. Levels of parasitaemia, red blood cell (RBC) counts, and survival times were followed in mice depleted of tumour necrosis factor (TCR)gamma delta+ or TCR alpha beta+ T cells. Numbers of gamma delta T cells increased in the spleens of control antibody-treated infected mice, but not in mice depleted of TCR gamma delta+ or TCR alpha beta+ T cells. Mice depleted of gamma delta T cells had levels of parasitaemia, RBCs, and survival rates similar to control antibody-treated mice. However, mice depleted of TCR alpha beta+ T cells had higher levels o...
Journal of immunology, 1980
ABSTRACT
The role of B lymphocytes in resistance to malaria was studied in defective and normal F1 mice de... more The role of B lymphocytes in resistance to malaria was studied in defective and normal F1 mice derived from CBA/N mice, a strain with an X-linked B cell defect. When infected with normally nonlethal Plasmodium yoelii, immune defective F1 male mice had higher parasitemias and more prolonged infections than normal F1 mice, as well as a 50% mortality rate. Before infection the plasma levels of IgM and IgG were lower in defective F1 males than normal F1 mice. The polyclonal IgM and IgG responses of infected abnormal F1 mice were delayed and lower in absolute magnitude than those of normal F1 mice. Furthermore, specific IgM and IgG anti-plasmodial antibody titers, as determined by radioimmunoassay, were depressed on day 12 in the defective F1 males. Although IgG titers approached those of the normal F1 mice on day 19, defective F1 male IgM titers remained depressed. These data demonstrate that an X-linked gene that affects B cell function influences malarial resistance in mice, presumabl...
Immunology, 1996
Although gamma delta T cells are found in increased numbers in the spleens of humans and mice inf... more Although gamma delta T cells are found in increased numbers in the spleens of humans and mice infected with malaria, it is not known if these cells are necessary components of an effective immune response. The surface phenotype of spleen cells obtained from mice infected with avirulent Plasmodium chabaudi adami or virulent Plasmodium chabaudi chabaudi were examined using anti-delta or anti-alpha beta T-cell-specific reagents and flow cytometry. Levels of parasitaemia, red blood cell (RBC) counts, and survival times were followed in mice depleted of tumour necrosis factor (TCR)gamma delta+ or TCR alpha beta+ T cells. Numbers of gamma delta T cells increased in the spleens of control antibody-treated infected mice, but not in mice depleted of TCR gamma delta+ or TCR alpha beta+ T cells. Mice depleted of gamma delta T cells had levels of parasitaemia, RBCs, and survival rates similar to control antibody-treated mice. However, mice depleted of TCR alpha beta+ T cells had higher levels o...
The Journal of Parasitology, 1983
The effects of six anthelmintics on larval stages of Nematospiroides dubius in mice were assessed... more The effects of six anthelmintics on larval stages of Nematospiroides dubius in mice were assessed. Levamisole phosphate, at a dose of 100 mg/kg administered per os 6 days postlarval inoculation (PI), effected greater than 98% reduction in worm burdens. At dose rates one log2 higher, 50% mortality of the mice occurred. Ivermectin, given per os at a dose rate of 5 mg/kg, removed all of the worms when administered either on Day 3 or 6 PI. No toxicity was observed even at the highest dose tested (25 mg/kg). Albendazole, cambendazole, pyrantel pamoate, and fenbendazole, all given per os at a dose of 100 mg/kg on day 6 PI, allowed from 52 to 75% of the worms to develop to adulthood. Ivermectin emerged as the larvicidal drug of choice owing to its high efficacy and undetectable toxic side effects.
Clinical and Experimental Immunology, 2004
Immunopharmacology, 1981
The influence of levamisole (LMS) on the primary immunoglobulin M (IgM antibody response of suckl... more The influence of levamisole (LMS) on the primary immunoglobulin M (IgM antibody response of suckling rats was investigated. Although suckling rats did make a direct plaque-forming cell (PFC) response to sheep red blood cells (SRBC), the magnitude of this response was much lower than that of adult rats. LMS treatment (2.5 mg/kg) markedly potentiated the anti-SRBC response in 10-day-old rats, but this enhanced PFC response never attained adult levels. In contrast, LMS failed to boost the anti-SRBC response of adult rats, although the adult response to suboptimal antigenic stimuli was enhanced. The ontogeny of immunological responsiveness to SRBC was not influenced by LMS; only existing responses could be modulated. The potentiating effect of LMS was dose-dependent, with high doses causing suppression. The influence of LMS did not involve the earlier appearance of PFC. Since LMS augmented the PFC response to SRBC when administered before or after antigen, it appears that both the induc...
Journal of immunology (Baltimore, Md. : 1950), 1979
The role of B lymphocytes in resistance to malaria was studied in defective and normal F1 mice de... more The role of B lymphocytes in resistance to malaria was studied in defective and normal F1 mice derived from CBA/N mice, a strain with an X-linked B cell defect. When infected with normally nonlethal Plasmodium yoelii, immune defective F1 male mice had higher parasitemias and more prolonged infections than normal F1 mice, as well as a 50% mortality rate. Before infection the plasma levels of IgM and IgG were lower in defective F1 males than normal F1 mice. The polyclonal IgM and IgG responses of infected abnormal F1 mice were delayed and lower in absolute magnitude than those of normal F1 mice. Furthermore, specific IgM and IgG anti-plasmodial antibody titers, as determined by radioimmunoassay, were depressed on day 12 in the defective F1 males. Although IgG titers approached those of the normal F1 mice on day 19, defective F1 male IgM titers remained depressed. These data demonstrate that an X-linked gene that affects B cell function influences malarial resistance in mice, presumabl...
Tropenmedizin und Parasitologie, 1979
Infection and immunity, 1977
The immunodepressive effect of Toxoplasma gondii infection in mice was studied, using sheep eryth... more The immunodepressive effect of Toxoplasma gondii infection in mice was studied, using sheep erythrocytes (SRBC) as the testing antigen and serum hemagglutinins, hemolysins, and both direct and indirect splenic plaque-forming cells (PFC) to SRBC as assays. In the primary antibody response, immunoglobulin M (IgM), hemagglutinins, and hemolysins and both IgM- and IgG-secreting PFC were depressed in animals immunized after infection. Maximum immunodepression occurred during the first 3 weeks of Toxoplasma infection. When the secondary antibody response was studied, results varied. Mice immunized with SRBC after being infected with T. gondii had a depression in both IgM and IgG PFC. Mice immunized with SRBC before being infected with T. gondii and then given a challenge dose of SRBC had a delay, but no an actual depression, in IgG hemagglutinins and hemolysins and IgG-secreting PFC. These studies show that the immunodepression associated with Toxoplasma infection is complicated, and they...
Nature immunology, 2000
Although B cells produce cytokines it is not known whether B cells can differentiate into effecto... more Although B cells produce cytokines it is not known whether B cells can differentiate into effector subsets that secrete polarized arrays of cytokines. We have identified two populations of "effector" B cells (Be1 and Be2) that produce distinct patterns of cytokines depending on the cytokine environment in which the cells were stimulated during their primary encounter with antigen and T cells. These effector B cell subsets subsequently regulate the differentiation of naïve CD4+ T cells to TH1 and TH2 cells through production of polarizing cytokines such as interleukin 4 and interferon gamma. In addition, Be1 and Be2 cells could be identified in animals that were infected with pathogens that preferentially induce a Type 1 and Type 2 immune response. Together these results suggest that, in addition to their well defined role in antibody production, B cells may regulate immune responses to infectious pathogens through their production of cytokines.
Natural immunity
Studies were performed to determine whether resistance to Toxoplasma gondii infection in mice dep... more Studies were performed to determine whether resistance to Toxoplasma gondii infection in mice depends on a mechanism involving neutrophils. Immunocompetent C57BL/6 and C.B-17 mice infected with T. gondii by gavage had an increased percentage of neutrophils in their peripheral blood. C57BL/6 mice selectively depleted of neutrophils by injections of RB6-8C5 monoclonal antibody died during the acute phase of the disease. Depletion of neutrophils had no effect on interferon gamma production, but had a profound effect on the total numbers of peripheral blood CD4+ and CD8+ T cells. Neutrophil-depleted C.B-17 mice survived longer than neutrophil-depleted C57BL/6 mice when infected with T. gondii, however they became much sicker, and were less able to survive long-term than infected, control mAb-treated mice as indicated by severe sustained weight loss. This study shows that neutrophils play an important role in resistance to acute primary T. gondii infection and that depletion of neutrophi...
Infection and immunity, 1996
The ts-4 strain of Toxoplasma gondii is a temperature-sensitive mutant that fails to grow at 40 d... more The ts-4 strain of Toxoplasma gondii is a temperature-sensitive mutant that fails to grow at 40 degrees C in vitro. Unlike mildly virulent cyst-forming strains, which can cause fatal chronic infections in certain mouse strains, ts-4 has been widely used to vaccinate mice against virulent T. gondii and is a valuable tool with which to investigate mechanisms of acquired resistance to this parasite. In this report, the basis for the avirulence of ts-4 is analyzed. It is shown that ts-4 is able to persist long-term in vivo in mildly immunocompromised mice, which rules out an intrinsic growth defect as a reason for avirulence. ts-4 does not induce body temperatures in mice as high as that needed to kill it in vitro. Moreover, the mild fevers elicited in resistant B6 mice are also seen in susceptible C57BL/6 scid/scid mice. However, ts-4 elicits strong preimmune defenses, dependent on gamma interferon, which are needed by mice to survive acute infection. Furthermore, CD4+ and CD8+ T-cell-...
Natural immunity, 1995
That strong cytolytic activity of natural killer (NK) cells is neither necessary nor sufficient f... more That strong cytolytic activity of natural killer (NK) cells is neither necessary nor sufficient for defense against acute Toxoplasma gondii infection is demonstrated. T. gondii-infected anti-interferon (IFN)-gamma-treated mice and IFN-gamma gene knockout mice died despite good induction of NK activity, while infected beige mice, deficient in NK cytolytic activity, survived.
Infection and immunity, 1996
Studies were performed to determine whether resistance to acute Toxoplasma gondii infection in mi... more Studies were performed to determine whether resistance to acute Toxoplasma gondii infection in mice depends on a mechanism involving CR3, the type 3 complement receptor. Nineteen of 22 mice (86%) given multiple injections of the anti-CR3 monoclonal antibody, 5C6, prior to and after intraperitoneal inoculation of cysts of the ordinarily mildly virulent ME49 strain of T. gondii died within 8 to 12 days, whereas control antibody-treated mice survived. All (five of five) anti-CR3-treated BALB/c mice infected via the natural peroral route died within 8 days of infection. Flow cytometric analysis of cells recovered from peritoneal lavages of anti-CR3-treated T. gondii-infected mice revealed that the percentage of Thy-1+ CD4- CD8- cells was reduced to about 50% of that of control antibody-treated mice and to about 20% of the number of such cells in controls. The numbers of macrophages, polymorphonuclear leukocytes, and lymphocytes recovered from the peritoneal cavities of T. gondii-infecte...
Journal of immunology (Baltimore, Md. : 1950), 1988
Inbred and H-2 congenic mouse strains were tested for their ability to resist infections with the... more Inbred and H-2 congenic mouse strains were tested for their ability to resist infections with the non-lethal 17X or with the lethal YM isolates of Plasmodium yoelii. DBA/2 and B10.D2 mice, which best resisted infections with non-lethal P. yoelii, were exquisitely susceptible to infection with lethal isolates of this malaria species. In contrast, B6 and B10 mice, which were susceptible to infection with non-lethal P. yoelii, were resistant to infection with the lethal isolates. This reversal of host response phenotype was influenced by H-2 genes, as evidenced by the divergent responses of the H-2 congenic strains B10 and B10.D2. However, a survey of mouse strains sharing common H-2 genes, but expressing different genetic backgrounds, demonstrated that genes outside the H-2 complex also influence the outcome of P. yoelii infections. By enumerating the numbers of P. yoelii-specific antibody-secreting cells in the spleens of infected mice, it was demonstrated that B6 mice, although susc...
The American Journal of Tropical Medicine and Hygiene, 1991
The role of the spleen in resistance to infections with nonlethal Plasmodium yoelii 17x is depend... more The role of the spleen in resistance to infections with nonlethal Plasmodium yoelii 17x is dependent upon the genotype of the host. Thus, DBA/2 (D2) mice infected with P. yoelii 17x were not adversely affected by removal of the spleen, while splenectomized C57BL/6 (B6) or Balb/c mice failed to resolve their infections and eventually died. The levels of parasitemia were lower in splenectomized mice compared to intact controls; however, splenectomized mice became as anemic as did spleen-intact controls. Splenectomy resulted in the appearance of large aggregates of mononuclear cells in the livers of infected mice and also altered the liver/body weight ratios. These results indicate that D2 mice have a spleen-independent mechanism of clearing parasites which is lacking in B6 and Balb/c mice.
Toxoplasma gondii infection in mice. CR3-dependent resistance to acute
The Journal of Immunology, 2007
Infection and Immunity, 1977
The immunodepressive effect of Toxoplasma gondii infection in mice was studied, using sheep eryth... more The immunodepressive effect of Toxoplasma gondii infection in mice was studied, using sheep erythrocytes (SRBC) as the testing antigen and serum hemagglutinins, hemolysins, and both direct and indirect splenic plaque-forming cells (PFC) to SRBC as assays. In the primary antibody response, immunoglobulin M (IgM), hemagglutinins, and hemolysins and both IgM- and IgG-secreting PFC were depressed in animals immunized after infection. Maximum immunodepression occurred during the first 3 weeks of Toxoplasma infection. When the secondary antibody response was studied, results varied. Mice immunized with SRBC after being infected with T. gondii had a depression in both IgM and IgG PFC. Mice immunized with SRBC before being infected with T. gondii and then given a challenge dose of SRBC had a delay, but no an actual depression, in IgG hemagglutinins and hemolysins and IgG-secreting PFC. These studies show that the immunodepression associated with Toxoplasma infection is complicated, and they...
Immunology, 1996
Although gamma delta T cells are found in increased numbers in the spleens of humans and mice inf... more Although gamma delta T cells are found in increased numbers in the spleens of humans and mice infected with malaria, it is not known if these cells are necessary components of an effective immune response. The surface phenotype of spleen cells obtained from mice infected with avirulent Plasmodium chabaudi adami or virulent Plasmodium chabaudi chabaudi were examined using anti-delta or anti-alpha beta T-cell-specific reagents and flow cytometry. Levels of parasitaemia, red blood cell (RBC) counts, and survival times were followed in mice depleted of tumour necrosis factor (TCR)gamma delta+ or TCR alpha beta+ T cells. Numbers of gamma delta T cells increased in the spleens of control antibody-treated infected mice, but not in mice depleted of TCR gamma delta+ or TCR alpha beta+ T cells. Mice depleted of gamma delta T cells had levels of parasitaemia, RBCs, and survival rates similar to control antibody-treated mice. However, mice depleted of TCR alpha beta+ T cells had higher levels o...
Journal of immunology, 1980
ABSTRACT
The role of B lymphocytes in resistance to malaria was studied in defective and normal F1 mice de... more The role of B lymphocytes in resistance to malaria was studied in defective and normal F1 mice derived from CBA/N mice, a strain with an X-linked B cell defect. When infected with normally nonlethal Plasmodium yoelii, immune defective F1 male mice had higher parasitemias and more prolonged infections than normal F1 mice, as well as a 50% mortality rate. Before infection the plasma levels of IgM and IgG were lower in defective F1 males than normal F1 mice. The polyclonal IgM and IgG responses of infected abnormal F1 mice were delayed and lower in absolute magnitude than those of normal F1 mice. Furthermore, specific IgM and IgG anti-plasmodial antibody titers, as determined by radioimmunoassay, were depressed on day 12 in the defective F1 males. Although IgG titers approached those of the normal F1 mice on day 19, defective F1 male IgM titers remained depressed. These data demonstrate that an X-linked gene that affects B cell function influences malarial resistance in mice, presumabl...
Immunology, 1996
Although gamma delta T cells are found in increased numbers in the spleens of humans and mice inf... more Although gamma delta T cells are found in increased numbers in the spleens of humans and mice infected with malaria, it is not known if these cells are necessary components of an effective immune response. The surface phenotype of spleen cells obtained from mice infected with avirulent Plasmodium chabaudi adami or virulent Plasmodium chabaudi chabaudi were examined using anti-delta or anti-alpha beta T-cell-specific reagents and flow cytometry. Levels of parasitaemia, red blood cell (RBC) counts, and survival times were followed in mice depleted of tumour necrosis factor (TCR)gamma delta+ or TCR alpha beta+ T cells. Numbers of gamma delta T cells increased in the spleens of control antibody-treated infected mice, but not in mice depleted of TCR gamma delta+ or TCR alpha beta+ T cells. Mice depleted of gamma delta T cells had levels of parasitaemia, RBCs, and survival rates similar to control antibody-treated mice. However, mice depleted of TCR alpha beta+ T cells had higher levels o...
The Journal of Parasitology, 1983
The effects of six anthelmintics on larval stages of Nematospiroides dubius in mice were assessed... more The effects of six anthelmintics on larval stages of Nematospiroides dubius in mice were assessed. Levamisole phosphate, at a dose of 100 mg/kg administered per os 6 days postlarval inoculation (PI), effected greater than 98% reduction in worm burdens. At dose rates one log2 higher, 50% mortality of the mice occurred. Ivermectin, given per os at a dose rate of 5 mg/kg, removed all of the worms when administered either on Day 3 or 6 PI. No toxicity was observed even at the highest dose tested (25 mg/kg). Albendazole, cambendazole, pyrantel pamoate, and fenbendazole, all given per os at a dose of 100 mg/kg on day 6 PI, allowed from 52 to 75% of the worms to develop to adulthood. Ivermectin emerged as the larvicidal drug of choice owing to its high efficacy and undetectable toxic side effects.
Clinical and Experimental Immunology, 2004
Immunopharmacology, 1981
The influence of levamisole (LMS) on the primary immunoglobulin M (IgM antibody response of suckl... more The influence of levamisole (LMS) on the primary immunoglobulin M (IgM antibody response of suckling rats was investigated. Although suckling rats did make a direct plaque-forming cell (PFC) response to sheep red blood cells (SRBC), the magnitude of this response was much lower than that of adult rats. LMS treatment (2.5 mg/kg) markedly potentiated the anti-SRBC response in 10-day-old rats, but this enhanced PFC response never attained adult levels. In contrast, LMS failed to boost the anti-SRBC response of adult rats, although the adult response to suboptimal antigenic stimuli was enhanced. The ontogeny of immunological responsiveness to SRBC was not influenced by LMS; only existing responses could be modulated. The potentiating effect of LMS was dose-dependent, with high doses causing suppression. The influence of LMS did not involve the earlier appearance of PFC. Since LMS augmented the PFC response to SRBC when administered before or after antigen, it appears that both the induc...
Journal of immunology (Baltimore, Md. : 1950), 1979
The role of B lymphocytes in resistance to malaria was studied in defective and normal F1 mice de... more The role of B lymphocytes in resistance to malaria was studied in defective and normal F1 mice derived from CBA/N mice, a strain with an X-linked B cell defect. When infected with normally nonlethal Plasmodium yoelii, immune defective F1 male mice had higher parasitemias and more prolonged infections than normal F1 mice, as well as a 50% mortality rate. Before infection the plasma levels of IgM and IgG were lower in defective F1 males than normal F1 mice. The polyclonal IgM and IgG responses of infected abnormal F1 mice were delayed and lower in absolute magnitude than those of normal F1 mice. Furthermore, specific IgM and IgG anti-plasmodial antibody titers, as determined by radioimmunoassay, were depressed on day 12 in the defective F1 males. Although IgG titers approached those of the normal F1 mice on day 19, defective F1 male IgM titers remained depressed. These data demonstrate that an X-linked gene that affects B cell function influences malarial resistance in mice, presumabl...
Tropenmedizin und Parasitologie, 1979
Infection and immunity, 1977
The immunodepressive effect of Toxoplasma gondii infection in mice was studied, using sheep eryth... more The immunodepressive effect of Toxoplasma gondii infection in mice was studied, using sheep erythrocytes (SRBC) as the testing antigen and serum hemagglutinins, hemolysins, and both direct and indirect splenic plaque-forming cells (PFC) to SRBC as assays. In the primary antibody response, immunoglobulin M (IgM), hemagglutinins, and hemolysins and both IgM- and IgG-secreting PFC were depressed in animals immunized after infection. Maximum immunodepression occurred during the first 3 weeks of Toxoplasma infection. When the secondary antibody response was studied, results varied. Mice immunized with SRBC after being infected with T. gondii had a depression in both IgM and IgG PFC. Mice immunized with SRBC before being infected with T. gondii and then given a challenge dose of SRBC had a delay, but no an actual depression, in IgG hemagglutinins and hemolysins and IgG-secreting PFC. These studies show that the immunodepression associated with Toxoplasma infection is complicated, and they...
Nature immunology, 2000
Although B cells produce cytokines it is not known whether B cells can differentiate into effecto... more Although B cells produce cytokines it is not known whether B cells can differentiate into effector subsets that secrete polarized arrays of cytokines. We have identified two populations of "effector" B cells (Be1 and Be2) that produce distinct patterns of cytokines depending on the cytokine environment in which the cells were stimulated during their primary encounter with antigen and T cells. These effector B cell subsets subsequently regulate the differentiation of naïve CD4+ T cells to TH1 and TH2 cells through production of polarizing cytokines such as interleukin 4 and interferon gamma. In addition, Be1 and Be2 cells could be identified in animals that were infected with pathogens that preferentially induce a Type 1 and Type 2 immune response. Together these results suggest that, in addition to their well defined role in antibody production, B cells may regulate immune responses to infectious pathogens through their production of cytokines.
Natural immunity
Studies were performed to determine whether resistance to Toxoplasma gondii infection in mice dep... more Studies were performed to determine whether resistance to Toxoplasma gondii infection in mice depends on a mechanism involving neutrophils. Immunocompetent C57BL/6 and C.B-17 mice infected with T. gondii by gavage had an increased percentage of neutrophils in their peripheral blood. C57BL/6 mice selectively depleted of neutrophils by injections of RB6-8C5 monoclonal antibody died during the acute phase of the disease. Depletion of neutrophils had no effect on interferon gamma production, but had a profound effect on the total numbers of peripheral blood CD4+ and CD8+ T cells. Neutrophil-depleted C.B-17 mice survived longer than neutrophil-depleted C57BL/6 mice when infected with T. gondii, however they became much sicker, and were less able to survive long-term than infected, control mAb-treated mice as indicated by severe sustained weight loss. This study shows that neutrophils play an important role in resistance to acute primary T. gondii infection and that depletion of neutrophi...
Infection and immunity, 1996
The ts-4 strain of Toxoplasma gondii is a temperature-sensitive mutant that fails to grow at 40 d... more The ts-4 strain of Toxoplasma gondii is a temperature-sensitive mutant that fails to grow at 40 degrees C in vitro. Unlike mildly virulent cyst-forming strains, which can cause fatal chronic infections in certain mouse strains, ts-4 has been widely used to vaccinate mice against virulent T. gondii and is a valuable tool with which to investigate mechanisms of acquired resistance to this parasite. In this report, the basis for the avirulence of ts-4 is analyzed. It is shown that ts-4 is able to persist long-term in vivo in mildly immunocompromised mice, which rules out an intrinsic growth defect as a reason for avirulence. ts-4 does not induce body temperatures in mice as high as that needed to kill it in vitro. Moreover, the mild fevers elicited in resistant B6 mice are also seen in susceptible C57BL/6 scid/scid mice. However, ts-4 elicits strong preimmune defenses, dependent on gamma interferon, which are needed by mice to survive acute infection. Furthermore, CD4+ and CD8+ T-cell-...
Natural immunity, 1995
That strong cytolytic activity of natural killer (NK) cells is neither necessary nor sufficient f... more That strong cytolytic activity of natural killer (NK) cells is neither necessary nor sufficient for defense against acute Toxoplasma gondii infection is demonstrated. T. gondii-infected anti-interferon (IFN)-gamma-treated mice and IFN-gamma gene knockout mice died despite good induction of NK activity, while infected beige mice, deficient in NK cytolytic activity, survived.
Infection and immunity, 1996
Studies were performed to determine whether resistance to acute Toxoplasma gondii infection in mi... more Studies were performed to determine whether resistance to acute Toxoplasma gondii infection in mice depends on a mechanism involving CR3, the type 3 complement receptor. Nineteen of 22 mice (86%) given multiple injections of the anti-CR3 monoclonal antibody, 5C6, prior to and after intraperitoneal inoculation of cysts of the ordinarily mildly virulent ME49 strain of T. gondii died within 8 to 12 days, whereas control antibody-treated mice survived. All (five of five) anti-CR3-treated BALB/c mice infected via the natural peroral route died within 8 days of infection. Flow cytometric analysis of cells recovered from peritoneal lavages of anti-CR3-treated T. gondii-infected mice revealed that the percentage of Thy-1+ CD4- CD8- cells was reduced to about 50% of that of control antibody-treated mice and to about 20% of the number of such cells in controls. The numbers of macrophages, polymorphonuclear leukocytes, and lymphocytes recovered from the peritoneal cavities of T. gondii-infecte...