Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4‐1BB), and their role in the generation of anti‐tumor immune responses
This study addresses the relative importance of CD134 (OX40) and CD137 (4‐1BB) in the costimulation of CD4+ and CD8+ T cells under comparable conditions of antigenic stimulation. We demonstrate that CD134 is capable of directly costimulating CD8+ T cells. However, costimulation of CD8+ T cells by CD...
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| Veröffentlicht in: | European journal of immunology 2002-12, Vol.32 (12), p.3617-3627 |
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| container_title | European journal of immunology |
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| creator | Taraban, Vadim Y. Rowley, Tania F. O'Brien, Lyn Chan, H. T. Claude Haswell, Linsey E. Green, Michael H. A. Tutt, Alison L. Glennie, Martin J. Al‐Shamkhani, Aymen |
| description | This study addresses the relative importance of CD134 (OX40) and CD137 (4‐1BB) in the costimulation of CD4+ and CD8+ T cells under comparable conditions of antigenic stimulation. We demonstrate that CD134 is capable of directly costimulating CD8+ T cells. However, costimulation of CD8+ T cells by CD134 is less potent than that triggered by CD137. The higher costimulatory activity of CD137, when compared with CD134, correlates well with its faster expression kinetics and higher levels on CD8+ T cells. Furthermore, induction of CD137 expression on CD8+ T cells is highly sensitive to low levels of TCR stimulation, which is in contrast with CD134. Conversely, CD134 is more effective than CD137 in costimulating CD4+ T cells. This, however, could not be attributed to differential expression. We also demonstrate that the transient nature of CD134 and CD137 expression on activated CD4+ T cells is the resultof proteolytic shedding. Consistent with the greater ability of CD137 to costimulate CD8+ T cells, stimulation of CD137 in vivo is considerably more effective than CD134 in augmenting anti‐tumor immune responses. Therefore, agents that stimulate signaling via CD137 are likely to be more useful in clinical conditions where highly effective CD8+ CTL responses are required. |
| doi_str_mv | 10.1002/1521-4141(200212)32:12<3617::AID-IMMU3617>3.0.CO;2-M |
| format | Article |
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Conversely, CD134 is more effective than CD137 in costimulating CD4+ T cells. This, however, could not be attributed to differential expression. We also demonstrate that the transient nature of CD134 and CD137 expression on activated CD4+ T cells is the resultof proteolytic shedding. Consistent with the greater ability of CD137 to costimulate CD8+ T cells, stimulation of CD137 in vivo is considerably more effective than CD134 in augmenting anti‐tumor immune responses. Therefore, agents that stimulate signaling via CD137 are likely to be more useful in clinical conditions where highly effective CD8+ CTL responses are required.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/1521-4141(200212)32:12<3617::AID-IMMU3617>3.0.CO;2-M</identifier><identifier>PMID: 12516549</identifier><language>eng</language><publisher>Weinheim: WILEY‐VCH Verlag</publisher><subject>Animals ; Antigens - administration & dosage ; Antigens, CD ; CD4-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - immunology ; Costimulation ; Cytokines - biosynthesis ; Immunotherapy ; Lymphocyte Activation ; Metalloendopeptidases - metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Neoplasms, Experimental - immunology ; Ovalbumin - administration & dosage ; Ovalbumin - immunology ; Receptors, Nerve Growth Factor - metabolism ; Receptors, OX40 ; Receptors, Tumor Necrosis Factor - metabolism ; Signal Transduction ; T cell activation ; Tumor immunity ; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism ; Tumor Necrosis Factor Receptor Superfamily, Member 9</subject><ispartof>European journal of immunology, 2002-12, Vol.32 (12), p.3617-3627</ispartof><rights>2002 WILEY‐VCH Verlag GmbH & Co. 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T. Claude</creatorcontrib><creatorcontrib>Haswell, Linsey E.</creatorcontrib><creatorcontrib>Green, Michael H. A.</creatorcontrib><creatorcontrib>Tutt, Alison L.</creatorcontrib><creatorcontrib>Glennie, Martin J.</creatorcontrib><creatorcontrib>Al‐Shamkhani, Aymen</creatorcontrib><title>Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4‐1BB), and their role in the generation of anti‐tumor immune responses</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>This study addresses the relative importance of CD134 (OX40) and CD137 (4‐1BB) in the costimulation of CD4+ and CD8+ T cells under comparable conditions of antigenic stimulation. We demonstrate that CD134 is capable of directly costimulating CD8+ T cells. However, costimulation of CD8+ T cells by CD134 is less potent than that triggered by CD137. The higher costimulatory activity of CD137, when compared with CD134, correlates well with its faster expression kinetics and higher levels on CD8+ T cells. Furthermore, induction of CD137 expression on CD8+ T cells is highly sensitive to low levels of TCR stimulation, which is in contrast with CD134. Conversely, CD134 is more effective than CD137 in costimulating CD4+ T cells. This, however, could not be attributed to differential expression. We also demonstrate that the transient nature of CD134 and CD137 expression on activated CD4+ T cells is the resultof proteolytic shedding. Consistent with the greater ability of CD137 to costimulate CD8+ T cells, stimulation of CD137 in vivo is considerably more effective than CD134 in augmenting anti‐tumor immune responses. Therefore, agents that stimulate signaling via CD137 are likely to be more useful in clinical conditions where highly effective CD8+ CTL responses are required.</description><subject>Animals</subject><subject>Antigens - administration & dosage</subject><subject>Antigens, CD</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Costimulation</subject><subject>Cytokines - biosynthesis</subject><subject>Immunotherapy</subject><subject>Lymphocyte Activation</subject><subject>Metalloendopeptidases - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Knockout</subject><subject>Neoplasms, Experimental - immunology</subject><subject>Ovalbumin - administration & dosage</subject><subject>Ovalbumin - immunology</subject><subject>Receptors, Nerve Growth Factor - metabolism</subject><subject>Receptors, OX40</subject><subject>Receptors, Tumor Necrosis Factor - metabolism</subject><subject>Signal Transduction</subject><subject>T cell activation</subject><subject>Tumor immunity</subject><subject>Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism</subject><subject>Tumor Necrosis Factor Receptor Superfamily, Member 9</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkc1uEzEUhUcIREPhFZBXKJGY4Gt7fhwqpHbaQqSGbFIJVpbjuQOD5g97RpAdj8Cj8Ew8CZ4klBVCbGz5-NxzLH9BcAZ0DpSyFxAxCAUImDJ_BDbjbAHsjMeQLBbny8twuVrdjqdXfE7n2folC1f3gsnd2P1gQimIkMmUngSPnPtEKZVxJB8GJ8AiiCMhJ8GPq6-dRefKtiG6yYlpXV_WQ6X71u4IFgWa3pG2IP1HJJu318Siwc5fEjd0aAtdl9WO1Fhv0TqSXQIXZLp-J-hsHzcKCZmKn9--w8XF7Ple9FGlJbatkJTNPvgDNmh1Pz7CV-mmL_1AP9S-pqzroUFf67q2cegeBw8KXTl8ctxPg9vrq032JrxZv15m5zehEYlIQpMYSEDqlG5FlKPMJeQ5jbcy1nEOUMQyj5gxvBA8Mlx4K4dYGJZrmWJMNT8Nnh1yO9t-HtD1qi6dwarSDbaDUwlLx9-EfxohjWUEKffGzcFobOucxUJ1tqy13SmgakSuRnZqZKcOyBX3ml89ZKU8cvUbueKKqmytmFr52KfH_mFbY_4n9MjYG94fDF_KCnf_VfqXzjuN_wKpQ8cU</recordid><startdate>200212</startdate><enddate>200212</enddate><creator>Taraban, Vadim Y.</creator><creator>Rowley, Tania F.</creator><creator>O'Brien, Lyn</creator><creator>Chan, H. T. Claude</creator><creator>Haswell, Linsey E.</creator><creator>Green, Michael H. A.</creator><creator>Tutt, Alison L.</creator><creator>Glennie, Martin J.</creator><creator>Al‐Shamkhani, Aymen</creator><general>WILEY‐VCH Verlag</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200212</creationdate><title>Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4‐1BB), and their role in the generation of anti‐tumor immune responses</title><author>Taraban, Vadim Y. ; Rowley, Tania F. ; O'Brien, Lyn ; Chan, H. T. Claude ; Haswell, Linsey E. ; Green, Michael H. 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T. Claude</creatorcontrib><creatorcontrib>Haswell, Linsey E.</creatorcontrib><creatorcontrib>Green, Michael H. A.</creatorcontrib><creatorcontrib>Tutt, Alison L.</creatorcontrib><creatorcontrib>Glennie, Martin J.</creatorcontrib><creatorcontrib>Al‐Shamkhani, Aymen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taraban, Vadim Y.</au><au>Rowley, Tania F.</au><au>O'Brien, Lyn</au><au>Chan, H. T. Claude</au><au>Haswell, Linsey E.</au><au>Green, Michael H. A.</au><au>Tutt, Alison L.</au><au>Glennie, Martin J.</au><au>Al‐Shamkhani, Aymen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4‐1BB), and their role in the generation of anti‐tumor immune responses</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2002-12</date><risdate>2002</risdate><volume>32</volume><issue>12</issue><spage>3617</spage><epage>3627</epage><pages>3617-3627</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><abstract>This study addresses the relative importance of CD134 (OX40) and CD137 (4‐1BB) in the costimulation of CD4+ and CD8+ T cells under comparable conditions of antigenic stimulation. We demonstrate that CD134 is capable of directly costimulating CD8+ T cells. However, costimulation of CD8+ T cells by CD134 is less potent than that triggered by CD137. The higher costimulatory activity of CD137, when compared with CD134, correlates well with its faster expression kinetics and higher levels on CD8+ T cells. Furthermore, induction of CD137 expression on CD8+ T cells is highly sensitive to low levels of TCR stimulation, which is in contrast with CD134. Conversely, CD134 is more effective than CD137 in costimulating CD4+ T cells. This, however, could not be attributed to differential expression. We also demonstrate that the transient nature of CD134 and CD137 expression on activated CD4+ T cells is the resultof proteolytic shedding. Consistent with the greater ability of CD137 to costimulate CD8+ T cells, stimulation of CD137 in vivo is considerably more effective than CD134 in augmenting anti‐tumor immune responses. Therefore, agents that stimulate signaling via CD137 are likely to be more useful in clinical conditions where highly effective CD8+ CTL responses are required.</abstract><cop>Weinheim</cop><pub>WILEY‐VCH Verlag</pub><pmid>12516549</pmid><doi>10.1002/1521-4141(200212)32:12<3617::AID-IMMU3617>3.0.CO;2-M</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Antigens - administration & dosage Antigens, CD CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Costimulation Cytokines - biosynthesis Immunotherapy Lymphocyte Activation Metalloendopeptidases - metabolism Mice Mice, Inbred BALB C Mice, Knockout Neoplasms, Experimental - immunology Ovalbumin - administration & dosage Ovalbumin - immunology Receptors, Nerve Growth Factor - metabolism Receptors, OX40 Receptors, Tumor Necrosis Factor - metabolism Signal Transduction T cell activation Tumor immunity Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism Tumor Necrosis Factor Receptor Superfamily, Member 9 |
| title | Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4‐1BB), and their role in the generation of anti‐tumor immune responses |
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