An epigenetic silencing pathway controlling T helper 2 cell lineage commitment
Identifieur interne : 005071 ( PascalFrancis/Curation ); précédent : 005070; suivant : 005072An epigenetic silencing pathway controlling T helper 2 cell lineage commitment
Auteurs : Rhys S. Allan [France] ; Elina Zueva [France] ; Florence Cammas [France] ; Heidi A. Schreiber [France, Australie, États-Unis] ; Vanessa Masson [France, Australie] ; Gabrielle T. Belz [Australie] ; Daniele Roche [France] ; Christele Maison [France] ; Jean-Pierre Quivy [France] ; Genevieve Almouzni [France] ; Sebastian Amigorena [France]Source :
- Nature : (London) [ 0028-0836 ] ; 2012.
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Abstract
During immune responses, naive CD4+ T cells differentiate into several T helper (TH) cell subsets under the control of lineage-specifying genes. These subsets (TH1, TH2 and TH17 cells and regulatory T cells) secrete distinct cytokines and are involved in protection against different types of infection. Epigenetic mechanisms are involved in the regulation of these developmental programs, and correlations have been drawn between the levels of particular epigenetic marks and the activity or silencing of specifying genes during differentiation1-3. Nevertheless, the functional relevance of the epigenetic pathways involved in TH cell subset differentiation and commitment is still unclear. Here we explore the role of the SUV39H1-H3K9me3-HP1α silencing pathway in the control of TH2 lineage stability. This pathway involves the histone methylase SUV39H1, which participates in the trimethylation of histone H3 on lysine 9 (H3K9me3), a modification that provides binding sites for heterochromatin protein 1α (HP1α)4,5 and promotes transcriptional silencing. This pathway was initially associated with heterochromatin formation and maintenance6 but can also contribute to the regulation of euchromatic genes7-9. We now propose that the SUV39H1-H3K9me3-HP1α pathway participates in maintaining the silencing of TH1 loci, ensuring TH2 lineage stability. In TH2 cells that are deficient in SUV39H1, the ratio between trimethylated and acetylated H3K9 is impaired, and the binding of HP1α at the promoters of silenced TH1 genes is reduced. Despite showing normal differentiation, both SUV39H1-deficient TH2 cells and HP1α-deficient TH2 cells, in contrast to wild-type cells, expressed TH1 genes when recultured under conditions that drive differentiation into TH1 cells. In a mouse model of TH2-driven allergic asthma, the chemical inhibition or loss of SUV39H1 skewed T-cell responses towards TH1 responses and decreased the lung pathology. These results establish a link between the SUV39H1-H3K9me3-HP1α pathway and the stability of TH2 cells, and they identify potential targets for therapeutic intervention in TH2-cell-mediated inflammatory diseases.
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Allan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM U932, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Zueva, Elina" sort="Zueva, Elina" uniqKey="Zueva E" first="Elina" last="Zueva">Elina Zueva</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM U932, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Cammas, Florence" sort="Cammas, Florence" uniqKey="Cammas F" first="Florence" last="Cammas">Florence Cammas</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut de Recherche en Cancérologie de Montpellier, CRLC Val d'Aurelle-Paul Lamarque</s1><s2>34298 Montpellier</s2><s3>FRA</s3><sZ>3 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Schreiber, Heidi A" sort="Schreiber, Heidi A" uniqKey="Schreiber H" first="Heidi A." last="Schreiber">Heidi A. Schreiber</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM U932, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Presentaddresses: Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Laboratory of Molecular Immunology and Rockefeller University, 1230 York Avenue</s1><s2>New York, New York 10065</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Masson, Vanessa" sort="Masson, Vanessa" uniqKey="Masson V" first="Vanessa" last="Masson">Vanessa Masson</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM U932, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Presentaddresses: Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Laboratory of Proteomic Mass Spectrometry, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Belz, Gabrielle T" sort="Belz, Gabrielle T" uniqKey="Belz G" first="Gabrielle T." last="Belz">Gabrielle T. 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aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Maison, Christele" sort="Maison, Christele" uniqKey="Maison C" first="Christele" last="Maison">Christele Maison</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>CNRS UMR218, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Quivy, Jean Pierre" sort="Quivy, Jean Pierre" uniqKey="Quivy J" first="Jean-Pierre" last="Quivy">Jean-Pierre Quivy</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>CNRS UMR218, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Almouzni, Genevieve" sort="Almouzni, Genevieve" uniqKey="Almouzni G" first="Genevieve" last="Almouzni">Genevieve Almouzni</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>CNRS UMR218, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Amigorena, Sebastian" sort="Amigorena, Sebastian" uniqKey="Amigorena S" first="Sebastian" last="Amigorena">Sebastian Amigorena</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM U932, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation></author></analytic><series><title level="j" type="main">Nature : (London)</title><title level="j" type="abbreviated">Nature : (Lond.)</title><idno type="ISSN">0028-0836</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Nature : (London)</title><title level="j" type="abbreviated">Nature : (Lond.)</title><idno type="ISSN">0028-0836</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Epigenetics</term><term>Gene silencing</term><term>Helper cell</term><term>Mouse</term><term>T-Lymphocyte</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Epigénétique</term><term>Silence expression génique</term><term>Cellule helper</term><term>Lymphocyte T</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">During immune responses, naive CD4<sup>+</sup> T cells differentiate into several T helper (T<sub>H</sub>) cell subsets under the control of lineage-specifying genes. These subsets (T<sub>H</sub>1, T<sub>H</sub>2 and T<sub>H</sub>17 cells and regulatory T cells) secrete distinct cytokines and are involved in protection against different types of infection. Epigenetic mechanisms are involved in the regulation of these developmental programs, and correlations have been drawn between the levels of particular epigenetic marks and the activity or silencing of specifying genes during differentiation<sup>1-3</sup>. Nevertheless, the functional relevance of the epigenetic pathways involved in T<sub>H</sub> cell subset differentiation and commitment is still unclear. Here we explore the role of the SUV39H1-H3K9me3-HP1α silencing pathway in the control of T<sub>H</sub>2 lineage stability. This pathway involves the histone methylase SUV39H1, which participates in the trimethylation of histone H3 on lysine 9 (H3K9me3), a modification that provides binding sites for heterochromatin protein 1α (HP1α)<sup>4,5</sup> and promotes transcriptional silencing. This pathway was initially associated with heterochromatin formation and maintenance<sup>6</sup> but can also contribute to the regulation of euchromatic genes<sup>7-9</sup>. We now propose that the SUV39H1-H3K9me3-HP1α pathway participates in maintaining the silencing of T<sub>H</sub>1 loci, ensuring T<sub>H</sub>2 lineage stability. In T<sub>H</sub>2 cells that are deficient in SUV39H1, the ratio between trimethylated and acetylated H3K9 is impaired, and the binding of HP1α at the promoters of silenced T<sub>H</sub>1 genes is reduced. Despite showing normal differentiation, both SUV39H1-deficient T<sub>H</sub>2 cells and HP1α-deficient T<sub>H</sub>2 cells, in contrast to wild-type cells, expressed T<sub>H</sub>1 genes when recultured under conditions that drive differentiation into T<sub>H</sub>1 cells. In a mouse model of T<sub>H</sub>2-driven allergic asthma, the chemical inhibition or loss of SUV39H1 skewed T-cell responses towards T<sub>H</sub>1 responses and decreased the lung pathology. These results establish a link between the SUV39H1-H3K9me3-HP1α pathway and the stability of T<sub>H</sub>2 cells, and they identify potential targets for therapeutic intervention in T<sub>H</sub>2-cell-mediated inflammatory diseases.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0028-0836</s0></fA01><fA02 i1="01"><s0>NATUAS</s0></fA02><fA03 i2="1"><s0>Nature : (Lond.)</s0></fA03><fA05><s2>487</s2></fA05><fA06><s2>7406</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>An epigenetic silencing pathway controlling T helper 2 cell lineage commitment</s1></fA08><fA11 i1="01" i2="1"><s1>ALLAN (Rhys S.)</s1></fA11><fA11 i1="02" i2="1"><s1>ZUEVA (Elina)</s1></fA11><fA11 i1="03" i2="1"><s1>CAMMAS (Florence)</s1></fA11><fA11 i1="04" i2="1"><s1>SCHREIBER (Heidi A.)</s1></fA11><fA11 i1="05" i2="1"><s1>MASSON (Vanessa)</s1></fA11><fA11 i1="06" i2="1"><s1>BELZ (Gabrielle T.)</s1></fA11><fA11 i1="07" i2="1"><s1>ROCHE (Daniele)</s1></fA11><fA11 i1="08" i2="1"><s1>MAISON (Christele)</s1></fA11><fA11 i1="09" i2="1"><s1>QUIVY (Jean-Pierre)</s1></fA11><fA11 i1="10" i2="1"><s1>ALMOUZNI (Genevieve)</s1></fA11><fA11 i1="11" i2="1"><s1>AMIGORENA (Sebastian)</s1></fA11><fA14 i1="01"><s1>Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></fA14><fA14 i1="02"><s1>INSERM U932, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>11 aut.</sZ></fA14><fA14 i1="03"><s1>Institut de Recherche en Cancérologie de Montpellier, CRLC Val d'Aurelle-Paul Lamarque</s1><s2>34298 Montpellier</s2><s3>FRA</s3><sZ>3 aut.</sZ></fA14><fA14 i1="04"><s1>Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>6 aut.</sZ></fA14><fA14 i1="05"><s1>CNRS UMR218, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="06"><s1>Presentaddresses: Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research</s1><s2>Parkville, Victoria 3052</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="07"><s1>Laboratory of Molecular Immunology and Rockefeller University, 1230 York Avenue</s1><s2>New York, New York 10065</s2><s3>USA</s3><sZ>4 aut.</sZ></fA14><fA14 i1="08"><s1>Laboratory of Proteomic Mass Spectrometry, Institut Curie Research Center, 26 rue d'Ulm</s1><s2>75248 Paris</s2><s3>FRA</s3><sZ>5 aut.</sZ></fA14><fA20><s1>249-253</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>142</s2><s5>354000505290400300</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>29 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0456078</s0></fA47><fA60><s1>P</s1><s3>CR</s3></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Nature : (London)</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>During immune responses, naive CD4<sup>+</sup> T cells differentiate into several T helper (T<sub>H</sub>) cell subsets under the control of lineage-specifying genes. These subsets (T<sub>H</sub>1, T<sub>H</sub>2 and T<sub>H</sub>17 cells and regulatory T cells) secrete distinct cytokines and are involved in protection against different types of infection. Epigenetic mechanisms are involved in the regulation of these developmental programs, and correlations have been drawn between the levels of particular epigenetic marks and the activity or silencing of specifying genes during differentiation<sup>1-3</sup>. Nevertheless, the functional relevance of the epigenetic pathways involved in T<sub>H</sub> cell subset differentiation and commitment is still unclear. Here we explore the role of the SUV39H1-H3K9me3-HP1α silencing pathway in the control of T<sub>H</sub>2 lineage stability. This pathway involves the histone methylase SUV39H1, which participates in the trimethylation of histone H3 on lysine 9 (H3K9me3), a modification that provides binding sites for heterochromatin protein 1α (HP1α)<sup>4,5</sup> and promotes transcriptional silencing. This pathway was initially associated with heterochromatin formation and maintenance<sup>6</sup> but can also contribute to the regulation of euchromatic genes<sup>7-9</sup>. We now propose that the SUV39H1-H3K9me3-HP1α pathway participates in maintaining the silencing of T<sub>H</sub>1 loci, ensuring T<sub>H</sub>2 lineage stability. In T<sub>H</sub>2 cells that are deficient in SUV39H1, the ratio between trimethylated and acetylated H3K9 is impaired, and the binding of HP1α at the promoters of silenced T<sub>H</sub>1 genes is reduced. Despite showing normal differentiation, both SUV39H1-deficient T<sub>H</sub>2 cells and HP1α-deficient T<sub>H</sub>2 cells, in contrast to wild-type cells, expressed T<sub>H</sub>1 genes when recultured under conditions that drive differentiation into T<sub>H</sub>1 cells. In a mouse model of T<sub>H</sub>2-driven allergic asthma, the chemical inhibition or loss of SUV39H1 skewed T-cell responses towards T<sub>H</sub>1 responses and decreased the lung pathology. These results establish a link between the SUV39H1-H3K9me3-HP1α pathway and the stability of T<sub>H</sub>2 cells, and they identify potential targets for therapeutic intervention in T<sub>H</sub>2-cell-mediated inflammatory diseases.</s0></fC01><fC02 i1="01" i2="X"><s0>002A04H03</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Epigénétique</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Epigenetics</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Epigenética</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Silence expression génique</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Gene silencing</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Silencio expresión genética</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Cellule helper</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Helper cell</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Célula auxiliar</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Lymphocyte T</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>T-Lymphocyte</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Linfocito T</s0><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Souris</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Mouse</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Ratón</s0><s5>05</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Vertebrata</s0><s2>NS</s2></fC07><fN21><s1>353</s1></fN21></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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