Edward Krug - Academia.edu (original) (raw)

Papers by Edward Krug

Research paper thumbnail of CD4-mediated and CD8-mediated cytotoxic and proliferative immune responses to Toxoplasma gondii in seropositive humans

Infection and …, Jan 1, 1996

Both CD4+ and CD8+ cytotoxic T lymphocytes (CTL) are part of the human immune response to Toxopla... more Both CD4+ and CD8+ cytotoxic T lymphocytes (CTL) are part of the human immune response to Toxoplasma gondii infection. To further our understanding of Toxoplasma immunity, we investigated factors influencing stimulation of CD4+ or CD8+ human T. gondii-specific immune cells. Both antigen-pulsed and Toxoplasma-infected antigen-presenting cells (APC) induced cell proliferation. Toxoplasma-infected APC elicited strong proliferation of CD4+ cells, but little or no proliferation of CD8+ cells, unless high antigen loads were used. Toxoplasma-infected APC stimulated specific cytotoxicity poorly or not at all, owing to death of stimulated cultures, whereas antigen-pulsed APC strongly elicited specific cytotoxicity. Cytotoxicity elicited by either type of APC resided exclusively in CD4+ T cells in polyclonal cultures. Thus, Toxoplasma-infected APC elicited stronger CD4-mediated than CD8-mediated cell proliferation and generated CD4+ CTL more readily than CD8+ CTL. Nonetheless, specific CD8+ memory cells were demonstrated, and rare CD8+ Toxoplasma-specific CTL were subcloned. Fixed Toxoplasma-infected APC (which induce CD8+ CTL) also elicited cell proliferation, but polyclonal cultures stimulated with these infected APC did not die. Unfixed Toxoplasma-infected APC strongly inhibited phytohemagglutinin-induced cell proliferation, whereas fixed APC did not. These data suggested that infected APC were inhibitory or lethal to some immune cells. Further investigations into interactions between immune cells and Toxoplasma-infected cells likely will help elucidate factors involved in the immunopathogenesis of Toxoplasma infection. As other intracellular parasites, including Plasmodium spp. and Leishmania spp., also elicit CD4+ CTL, such work may help establish paradigms governing immunity to intracellular parasites.

Research paper thumbnail of Cloned human CD4+ cytotoxic T lymphocytes specific for Toxoplasma gondii lyse tachyzoite-infected target cells

The Journal of …, Jan 1, 1993

Research paper thumbnail of Purine and pyrimidine metabolism

Page 103. Purine and Pyrimidine Metabolism RANDOLPH L. BERENS1, EDWARD C. KRUG1 and J. JOSEPH MAR... more Page 103. Purine and Pyrimidine Metabolism RANDOLPH L. BERENS1, EDWARD C. KRUG1 and J. JOSEPH MARR2 1Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO, USA and ...

Research paper thumbnail of Corticosteroids in serum of Rana catesbeiana during development and metamorphosis

General and comparative …, Jan 1, 1983

Radioimmunoassays (RIA) for aldosterone (ALDO), corticosterone (B), and cortisol (F) were used to... more Radioimmunoassays (RIA) for aldosterone (ALDO), corticosterone (B), and cortisol (F) were used to measure corticosteroids in serum of Rana catesbeiana tadpoles and of young and adult frogs. Because of the uncertain identity of the cortisol-like material in the RIA, it was designated "I!." Serum ALDO was detectable in tadpoles by stage VII and it remained at about 2 rig/ml in most stages until midclimax; then its concentration rose to high levels in froglets and frogs. Serum B appeared later in development (by stage XII) and its concentration increased rapidly to an initial peak at stage XVII. The B concentration increased again after midclimax coincident with the rise in ALDO. After stage XV serum B concentration was about 10 times higher than ALDO in most samples. Serum "F" was detectable by stage V and the concentration rose gradually to stage XIV; then it increased more rapidly until midclimax, whereupon its concentration fell precipitously to reach low levels in froglets and adults. A single injection of ACTH (0.1 III/tadpole) failed to increase serum ALDO, B, or "F" in premetamorphic larvae, but it caused a significant elevation of the two glucocorticoids in prometamorphic animals. Chronic treatment with ACTH or thyroxine (TJ increased the serum levels of the three steroids. Treatment with ACTH plus Tq markedly increased ALDO and B responses to the ACTH but the "F" response was diminished. We interpret the results to indicate that low levels of thyroid hormones (TH) sensitize the interrenal to stimulation by ACTH. Higher levels of TH and/or longer exposure to these hormones further enhance the ALDO and B responses while inhibiting the "F" response. The TH may also alter peripheral metabolism and/or clearance of the steroids to produce the changes which were observed. In either case, our results indicate that THinduced maturation of the hypothalamo-hypophyseal-interrenal axis contributes to the control of development and metamorphosis in anurans. The pattern of serum B and "F" appears to be related to developmental events, such as hind leg growth and gut and tail regression, but the serum pattern of ALDO did not show any such relationship. 232 0016-6480/83 $1.50

Research paper thumbnail of CD4-mediated and CD8-mediated cytotoxic and proliferative immune responses to Toxoplasma gondii in seropositive humans

Infection and …, Jan 1, 1996

Both CD4+ and CD8+ cytotoxic T lymphocytes (CTL) are part of the human immune response to Toxopla... more Both CD4+ and CD8+ cytotoxic T lymphocytes (CTL) are part of the human immune response to Toxoplasma gondii infection. To further our understanding of Toxoplasma immunity, we investigated factors influencing stimulation of CD4+ or CD8+ human T. gondii-specific immune cells. Both antigen-pulsed and Toxoplasma-infected antigen-presenting cells (APC) induced cell proliferation. Toxoplasma-infected APC elicited strong proliferation of CD4+ cells, but little or no proliferation of CD8+ cells, unless high antigen loads were used. Toxoplasma-infected APC stimulated specific cytotoxicity poorly or not at all, owing to death of stimulated cultures, whereas antigen-pulsed APC strongly elicited specific cytotoxicity. Cytotoxicity elicited by either type of APC resided exclusively in CD4+ T cells in polyclonal cultures. Thus, Toxoplasma-infected APC elicited stronger CD4-mediated than CD8-mediated cell proliferation and generated CD4+ CTL more readily than CD8+ CTL. Nonetheless, specific CD8+ memory cells were demonstrated, and rare CD8+ Toxoplasma-specific CTL were subcloned. Fixed Toxoplasma-infected APC (which induce CD8+ CTL) also elicited cell proliferation, but polyclonal cultures stimulated with these infected APC did not die. Unfixed Toxoplasma-infected APC strongly inhibited phytohemagglutinin-induced cell proliferation, whereas fixed APC did not. These data suggested that infected APC were inhibitory or lethal to some immune cells. Further investigations into interactions between immune cells and Toxoplasma-infected cells likely will help elucidate factors involved in the immunopathogenesis of Toxoplasma infection. As other intracellular parasites, including Plasmodium spp. and Leishmania spp., also elicit CD4+ CTL, such work may help establish paradigms governing immunity to intracellular parasites.

Research paper thumbnail of Cloned human CD4+ cytotoxic T lymphocytes specific for Toxoplasma gondii lyse tachyzoite-infected target cells

The Journal of …, Jan 1, 1993

Research paper thumbnail of Purine and pyrimidine metabolism

Page 103. Purine and Pyrimidine Metabolism RANDOLPH L. BERENS1, EDWARD C. KRUG1 and J. JOSEPH MAR... more Page 103. Purine and Pyrimidine Metabolism RANDOLPH L. BERENS1, EDWARD C. KRUG1 and J. JOSEPH MARR2 1Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO, USA and ...

Research paper thumbnail of Corticosteroids in serum of Rana catesbeiana during development and metamorphosis

General and comparative …, Jan 1, 1983

Radioimmunoassays (RIA) for aldosterone (ALDO), corticosterone (B), and cortisol (F) were used to... more Radioimmunoassays (RIA) for aldosterone (ALDO), corticosterone (B), and cortisol (F) were used to measure corticosteroids in serum of Rana catesbeiana tadpoles and of young and adult frogs. Because of the uncertain identity of the cortisol-like material in the RIA, it was designated "I!." Serum ALDO was detectable in tadpoles by stage VII and it remained at about 2 rig/ml in most stages until midclimax; then its concentration rose to high levels in froglets and frogs. Serum B appeared later in development (by stage XII) and its concentration increased rapidly to an initial peak at stage XVII. The B concentration increased again after midclimax coincident with the rise in ALDO. After stage XV serum B concentration was about 10 times higher than ALDO in most samples. Serum "F" was detectable by stage V and the concentration rose gradually to stage XIV; then it increased more rapidly until midclimax, whereupon its concentration fell precipitously to reach low levels in froglets and adults. A single injection of ACTH (0.1 III/tadpole) failed to increase serum ALDO, B, or "F" in premetamorphic larvae, but it caused a significant elevation of the two glucocorticoids in prometamorphic animals. Chronic treatment with ACTH or thyroxine (TJ increased the serum levels of the three steroids. Treatment with ACTH plus Tq markedly increased ALDO and B responses to the ACTH but the "F" response was diminished. We interpret the results to indicate that low levels of thyroid hormones (TH) sensitize the interrenal to stimulation by ACTH. Higher levels of TH and/or longer exposure to these hormones further enhance the ALDO and B responses while inhibiting the "F" response. The TH may also alter peripheral metabolism and/or clearance of the steroids to produce the changes which were observed. In either case, our results indicate that THinduced maturation of the hypothalamo-hypophyseal-interrenal axis contributes to the control of development and metamorphosis in anurans. The pattern of serum B and "F" appears to be related to developmental events, such as hind leg growth and gut and tail regression, but the serum pattern of ALDO did not show any such relationship. 232 0016-6480/83 $1.50