{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/39002"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/39002","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Positive and negative immunoregulation of normal and tumor-bearing mouse T cell blastogenesis","abstract":"Using the mixed lymphocyte reaction (MLR) as a correlate of cell-mediated immunity, an examination was made of positive and negative blastogenic immunoregulation by syngeneic peritoneal macrophages (M<sub>Φ</sub>) and splenic T cells from tumor-bearing mice (TBM). As analysis of T cell proliferative response progressed an intricate pattern of immunoregulatory checks and balances unfolded involving both M<sub>Φ</sub> and TBM cells. In their capacity as regulators, M<sub>Φ</sub> acted, not only to enhance MLR reactivity, but to inhibit it. Results indicated that: i) M<sub>Φ</sub> regulation was a concentration dependent phenomena -- high concentrations of M<sub>Φ</sub> (or their supernatants) inhibited MLR reactivity, while low doses enhanced MLR reactivity; ii) inhibition occurred via a non-toxic, heat stable, nondialyzable (and therefore non-thymidine) factor; iii) enhancement occurred via a heat labile nondialyzable factor. Since normal M<sub>Φ</sub> possessed a factor which, in high concentrations, inhibited T cell blastogenesis, tests were run to determine if the MLR hyporeactivity of T cells from TBM could be attributed to a unique tumor-induced inhibitory M<sub>Φ</sub>. Contrary to expectations, TBM M<sub>Φ</sub> supernatants, when compared to their normal counterparts on a volume-to-volume basis. showed an increased (not decreased) ability to enhance MLR reactivity. In light of results showing TBM M<sub>Φ</sub> enhancement of MLR reactivity, T cell hyporeactivity in TBM was explained after observation of the following dual regulatory mechanism of suppression: i) on a purely quantitative basis, the high in vivo concentration of M<sub>Φ</sub> in spleens of TBM inhibits spleen cell response to alloantigen; ii) there also exists a population of mildly nylon wool adherent tumor-induced splenic T cells which elaborate a soluble factor capable of overriding any M<sub>Φ</sub> enhancing effect. In their capacity as regulators, tumor-induced splenic T-cells act, both to enhance and inhibit MLR reactivity. Whereas M<sub>Φ</sub> regulation is concentration dependent, in the case of the T cell regulator, regulation is based, not upon the relative concentration of the regulator cell, but upon the level of responder cell activity, i.e. M<sub>Φ</sub>-depleted MLR cultures (showing minimal proliferation) were enhanced by regulator TEM T cell addition, while M<sub>Φ</sub> augmented MLR cultures or PHA stimulated cultures (with a high rate of blastogenesis) were inhibited by the same concentration of TBM regulator cells. Centering around more stringent biophysical and biochemical characterization of M<sub>Φ</sub> supernatants, the latest work has resulted in the biochemical separation of M<sub>Φ</sub> supernatants into inhibitor and enhancing components. Using anion exchange chromotography and slab gel electrophoresis, inhibitor and enhancing factors have been separated by charge. Treatment of M<sub>Φ</sub> with indomethacin did not abrogate release of inhibitor factor, suggesting that it was not prostaglandin. Enhancing factor, obtained from M<sub>Φ</sub> sonicates as well as supernatants, could be distinguished from lymphocyte activating factor by its inability to induce a thymocyte PHA response. Thus, analysis of regulation in the cell-mediated immune system has resulted in the elucidation of a most elaborate scheme of immunoregulation involving both M<sub>Φ</sub> and T cells.","abstract_html":"Using the mixed lymphocyte reaction (MLR) as a correlate of cell-mediated immunity, an examination was made of positive and negative blastogenic immunoregulation by syngeneic peritoneal macrophages (M&lt;sub&gt;Φ&lt;/sub&gt;) and splenic T cells from tumor-bearing mice (TBM). As analysis of T cell proliferative response progressed an intricate pattern of immunoregulatory checks and balances unfolded involving both M&lt;sub&gt;Φ&lt;/sub&gt; and TBM cells. In their capacity as regulators, M&lt;sub&gt;Φ&lt;/sub&gt; acted, not only to enhance MLR reactivity, but to inhibit it. Results indicated that: i) M&lt;sub&gt;Φ&lt;/sub&gt; regulation was a concentration dependent phenomena -- high concentrations of M&lt;sub&gt;Φ&lt;/sub&gt; (or their supernatants) inhibited MLR reactivity, while low doses enhanced MLR reactivity; ii) inhibition occurred via a non-toxic, heat stable, nondialyzable (and therefore non-thymidine) factor; iii) enhancement occurred via a heat labile nondialyzable factor. Since normal M&lt;sub&gt;Φ&lt;/sub&gt; possessed a factor which, in high concentrations, inhibited T cell blastogenesis, tests were run to determine if the MLR hyporeactivity of T cells from TBM could be attributed to a unique tumor-induced inhibitory M&lt;sub&gt;Φ&lt;/sub&gt;. Contrary to expectations, TBM M&lt;sub&gt;Φ&lt;/sub&gt; supernatants, when compared to their normal counterparts on a volume-to-volume basis. showed an increased (not decreased) ability to enhance MLR reactivity. In light of results showing TBM M&lt;sub&gt;Φ&lt;/sub&gt; enhancement of MLR reactivity, T cell hyporeactivity in TBM was explained after observation of the following dual regulatory mechanism of suppression: i) on a purely quantitative basis, the high in vivo concentration of M&lt;sub&gt;Φ&lt;/sub&gt; in spleens of TBM inhibits spleen cell response to alloantigen; ii) there also exists a population of mildly nylon wool adherent tumor-induced splenic T cells which elaborate a soluble factor capable of overriding any M&lt;sub&gt;Φ&lt;/sub&gt; enhancing effect. In their capacity as regulators, tumor-induced splenic T-cells act, both to enhance and inhibit MLR reactivity. Whereas M&lt;sub&gt;Φ&lt;/sub&gt; regulation is concentration dependent, in the case of the T cell regulator, regulation is based, not upon the relative concentration of the regulator cell, but upon the level of responder cell activity, i.e. M&lt;sub&gt;Φ&lt;/sub&gt;-depleted MLR cultures (showing minimal proliferation) were enhanced by regulator TEM T cell addition, while M&lt;sub&gt;Φ&lt;/sub&gt; augmented MLR cultures or PHA stimulated cultures (with a high rate of blastogenesis) were inhibited by the same concentration of TBM regulator cells. Centering around more stringent biophysical and biochemical characterization of M&lt;sub&gt;Φ&lt;/sub&gt; supernatants, the latest work has resulted in the biochemical separation of M&lt;sub&gt;Φ&lt;/sub&gt; supernatants into inhibitor and enhancing components. Using anion exchange chromotography and slab gel electrophoresis, inhibitor and enhancing factors have been separated by charge. Treatment of M&lt;sub&gt;Φ&lt;/sub&gt; with indomethacin did not abrogate release of inhibitor factor, suggesting that it was not prostaglandin. Enhancing factor, obtained from M&lt;sub&gt;Φ&lt;/sub&gt; sonicates as well as supernatants, could be distinguished from lymphocyte activating factor by its inability to induce a thymocyte PHA response. Thus, analysis of regulation in the cell-mediated immune system has resulted in the elucidation of a most elaborate scheme of immunoregulation involving both M&lt;sub&gt;Φ&lt;/sub&gt; and T cells.","abstract_has_math":false,"creators":["Connolly, Kevin Michael"],"institution":"Virginia Tech","degree_name":"Ph. D.","degree_level":"doctoral","degree_discipline":"Microbiology","degree_department":"Microbiology","school":null,"contributors":[],"advisors":[],"committee_chairs":["Elgert, Klaus D."],"committee_members":["Bates, Robert C.","Krieg, Noel R.","Conroy, James M.","Schurig, Gerhardt G."],"year":1979,"date_issued":"1979","date_published":"1979","updated_at":"2026-07-22T22:20:32Z","subjects":[],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-07282010-020423"],"render_values":[{"text":"etd-07282010-020423","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10919/39002","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Elgert, Klaus D."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Bates, Robert C.","Krieg, Noel R.","Conroy, James M.","Schurig, Gerhardt G."]},{"key":"dc:contributor.department","label":"Department","values":["Microbiology"]},{"key":"dc:creator","label":"Author","values":["Connolly, Kevin Michael"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2014-03-14T21:16:54Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2014-03-14T21:16:54Z","2010-07-28"]},{"key":"dc:date.issued","label":"Date","values":["1979"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"dc:type.dcmitype","label":"Dc Type Dcmitype","values":["Text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. 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As analysis of T cell proliferative response progressed an intricate pattern of immunoregulatory checks and balances unfolded involving both M<sub>Φ</sub> and TBM cells. In their capacity as regulators, M<sub>Φ</sub> acted, not only to enhance MLR reactivity, but to inhibit it. Results indicated that: i) M<sub>Φ</sub> regulation was a concentration dependent phenomena -- high concentrations of M<sub>Φ</sub> (or their supernatants) inhibited MLR reactivity, while low doses enhanced MLR reactivity; ii) inhibition occurred via a non-toxic, heat stable, nondialyzable (and therefore non-thymidine) factor; iii) enhancement occurred via a heat labile nondialyzable factor. Since normal M<sub>Φ</sub> possessed a factor which, in high concentrations, inhibited T cell blastogenesis, tests were run to determine if the MLR hyporeactivity of T cells from TBM could be attributed to a unique tumor-induced inhibitory M<sub>Φ</sub>. Contrary to expectations, TBM M<sub>Φ</sub> supernatants, when compared to their normal counterparts on a volume-to-volume basis. showed an increased (not decreased) ability to enhance MLR reactivity. In light of results showing TBM M<sub>Φ</sub> enhancement of MLR reactivity, T cell hyporeactivity in TBM was explained after observation of the following dual regulatory mechanism of suppression: i) on a purely quantitative basis, the high in vivo concentration of M<sub>Φ</sub> in spleens of TBM inhibits spleen cell response to alloantigen; ii) there also exists a population of mildly nylon wool adherent tumor-induced splenic T cells which elaborate a soluble factor capable of overriding any M<sub>Φ</sub> enhancing effect. In their capacity as regulators, tumor-induced splenic T-cells act, both to enhance and inhibit MLR reactivity. Whereas M<sub>Φ</sub> regulation is concentration dependent, in the case of the T cell regulator, regulation is based, not upon the relative concentration of the regulator cell, but upon the level of responder cell activity, i.e. M<sub>Φ</sub>-depleted MLR cultures (showing minimal proliferation) were enhanced by regulator TEM T cell addition, while M<sub>Φ</sub> augmented MLR cultures or PHA stimulated cultures (with a high rate of blastogenesis) were inhibited by the same concentration of TBM regulator cells. Centering around more stringent biophysical and biochemical characterization of M<sub>Φ</sub> supernatants, the latest work has resulted in the biochemical separation of M<sub>Φ</sub> supernatants into inhibitor and enhancing components. Using anion exchange chromotography and slab gel electrophoresis, inhibitor and enhancing factors have been separated by charge. Treatment of M<sub>Φ</sub> with indomethacin did not abrogate release of inhibitor factor, suggesting that it was not prostaglandin. Enhancing factor, obtained from M<sub>Φ</sub> sonicates as well as supernatants, could be distinguished from lymphocyte activating factor by its inability to induce a thymocyte PHA response. Thus, analysis of regulation in the cell-mediated immune system has resulted in the elucidation of a most elaborate scheme of immunoregulation involving both M<sub>Φ</sub> and T cells."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. D."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["BTD"]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Positive and negative immunoregulation of normal and tumor-bearing mouse T cell blastogenesis"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Elgert, Klaus D."],"dc:contributor.committeemember":["Bates, Robert C.","Krieg, Noel R.","Conroy, James M.","Schurig, Gerhardt G."],"dc:contributor.department":["Microbiology"],"dc:creator":["Connolly, Kevin Michael"],"dc:date.accessioned":["2014-03-14T21:16:54Z"],"dc:date.available":["2014-03-14T21:16:54Z","2010-07-28"],"dc:date.issued":["1979"],"dc:description.abstract":["Using the mixed lymphocyte reaction (MLR) as a correlate of cell-mediated immunity, an examination was made of positive and negative blastogenic immunoregulation by syngeneic peritoneal macrophages (M<sub>Φ</sub>) and splenic T cells from tumor-bearing mice (TBM). As analysis of T cell proliferative response progressed an intricate pattern of immunoregulatory checks and balances unfolded involving both M<sub>Φ</sub> and TBM cells. In their capacity as regulators, M<sub>Φ</sub> acted, not only to enhance MLR reactivity, but to inhibit it. Results indicated that: i) M<sub>Φ</sub> regulation was a concentration dependent phenomena -- high concentrations of M<sub>Φ</sub> (or their supernatants) inhibited MLR reactivity, while low doses enhanced MLR reactivity; ii) inhibition occurred via a non-toxic, heat stable, nondialyzable (and therefore non-thymidine) factor; iii) enhancement occurred via a heat labile nondialyzable factor. Since normal M<sub>Φ</sub> possessed a factor which, in high concentrations, inhibited T cell blastogenesis, tests were run to determine if the MLR hyporeactivity of T cells from TBM could be attributed to a unique tumor-induced inhibitory M<sub>Φ</sub>. Contrary to expectations, TBM M<sub>Φ</sub> supernatants, when compared to their normal counterparts on a volume-to-volume basis. showed an increased (not decreased) ability to enhance MLR reactivity. In light of results showing TBM M<sub>Φ</sub> enhancement of MLR reactivity, T cell hyporeactivity in TBM was explained after observation of the following dual regulatory mechanism of suppression: i) on a purely quantitative basis, the high in vivo concentration of M<sub>Φ</sub> in spleens of TBM inhibits spleen cell response to alloantigen; ii) there also exists a population of mildly nylon wool adherent tumor-induced splenic T cells which elaborate a soluble factor capable of overriding any M<sub>Φ</sub> enhancing effect. In their capacity as regulators, tumor-induced splenic T-cells act, both to enhance and inhibit MLR reactivity. Whereas M<sub>Φ</sub> regulation is concentration dependent, in the case of the T cell regulator, regulation is based, not upon the relative concentration of the regulator cell, but upon the level of responder cell activity, i.e. M<sub>Φ</sub>-depleted MLR cultures (showing minimal proliferation) were enhanced by regulator TEM T cell addition, while M<sub>Φ</sub> augmented MLR cultures or PHA stimulated cultures (with a high rate of blastogenesis) were inhibited by the same concentration of TBM regulator cells. Centering around more stringent biophysical and biochemical characterization of M<sub>Φ</sub> supernatants, the latest work has resulted in the biochemical separation of M<sub>Φ</sub> supernatants into inhibitor and enhancing components. Using anion exchange chromotography and slab gel electrophoresis, inhibitor and enhancing factors have been separated by charge. Treatment of M<sub>Φ</sub> with indomethacin did not abrogate release of inhibitor factor, suggesting that it was not prostaglandin. Enhancing factor, obtained from M<sub>Φ</sub> sonicates as well as supernatants, could be distinguished from lymphocyte activating factor by its inability to induce a thymocyte PHA response. Thus, analysis of regulation in the cell-mediated immune system has resulted in the elucidation of a most elaborate scheme of immunoregulation involving both M<sub>Φ</sub> and T cells."],"dc:description.degree":["Ph. D."],"dc:format.medium":["BTD"],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["etd-07282010-020423"],"dc:identifier.uri":["http://hdl.handle.net/10919/39002"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:title":["Positive and negative immunoregulation of normal and tumor-bearing mouse T cell blastogenesis"],"dc:type":["Dissertation"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Microbiology"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:20:32Z"}