ƉuÖ@FbՏpɂނ

<strong>RE씎</strong>
i񌤋Z^[[ÊJZ^[ ƉuTRj
emailF<a href="mailto:dsugiyam@east.ncc.go.jp">R</a>
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̈Zr[, <strong>4</strong>, e005 (2015)@<a href="http://dx.doi.org/10.7875/leading.author.4.e005">DOI: 10.7875/leading.author.4.e005</a>
Daisuke Sugiyama & Hiroyoshi Nishikawa: <strong>Cancer immunology: bench to bedside.</strong>

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<h2>v </h2>
@ߔNC̐VȎÖ@ƂĂƉuÖ@rтĂĎ_@ƂȂ̂́CRCTLA-4R̂эRPD-1R̂̎ÖƂďFꂽƂłD̈iC炾ɔƉun𑀍삵CrƉu͂邱Ƃɂ肪ÂD́gƉuɂ肪rhƂTOiɂȂƂ́C܂ł̂񎡗ÂɐVȑI炵D̃r[ł́C܂ł̂ƉuwɂbЉCbՏpւ̋n̐ĈƉuÖ@̐iWɂčl@D

<h2>͂߂</h2>
@݂ł́C2l1l𔭏ǂC3l1lɂ莀SƂ̓vZoĂD̎Ö@͓XiĂCѐ͌サĂDȂCˑRƂĂɂ鎀S͏㏸ÂĂCVȎÖ@̊JƂ߂ĂD̂ȂŁCƉuÖ@̐VȎÖ@ƂĒڂĂDqgɂĂ1ɐ̂זEĂƂĂ邪CK炷ׂĂ̔ǂɂ͒ȂD̗R̂ЂƂ́C炾ɔƉu@\̂זErĂ邩łD̂炾ɂẮCrƉu@\Ƃ񂪐т@\Ƃ˂ɝhRĂCoX҂ɂނƂɂ肪񂪔ǂD̃r[ł́C̔rɂƉu@\т̐菕Ɖu@\ɒڂCƉu`FbN|Cg^pN𒆐SɉD

<h2>1DƉuÖ@̗j</h2>
@\N̂ɁCƉuÖ@݂̑ɍLmC}ɔWČȂ悤ɂȂDߏȖƉuɂ肪񂪔rƂۂ́COłɊᇂ̊҂ɂĎᇂ̑ޏkmFꂽƂ1868N̕񍐂NƂĂ<a href="#R1"><sup>1)</sup></a>D̂̂1893Nɂ́COł̌łAۂ̒ɂ錃Ɖu𗘗pC؏s\̈ᇂɑ΂鎡Â{ꂽ<a href="#R2"><sup>2)</sup></a>D̎ۂCƉun̔}Ƃ1909Nɂ͂߂Ē񏥂ꂽD̂̂1950N1970NɂCƉunזEr邱Ƃɂ肪̔}ĂƂgcancer immunosurveillancehƂl񏥂ꂽC1974NɁCk[h}EXiƉusS}EXjpɂĖƉun̗Lɂ蔭ɍق݂͂ȂƂ񍐂CƉǔ͌ނD̂ɁCk[h}EX͊SȖƉusSĂ炸CƉusSRAGmbNAEg}EXpɂĖƉuɂ锭̒x؂ƂƂɁCqĝR̔ɂ肪Ɖǔ͂ӂѐiW邱ƂɂȂ<a href="#R3"><sup>3)</sup></a>D݂ł́CCTLA-4PD-1ƂƉu`FbN|Cg^pŇCᇂ̋ǏɂƉuזE̋@\Ɋւ錤ȂǁCLpi߂ĂD

<h2>2DƉuɊ֗^ƉuזE</h2>
@Ɖuɂ͂܂܂ȖƉuזE֗^ĂCזE̋쒀SזEƂזE̐ёBזEƂ݂DO҂ɂ̓L[TזEiCD8zTזEjCi`L[זECזEC}Nt@[W܂܂C҂ɂ͐䐫TזECR}זE܂܂D
@̔ɂ̓i`L[זEɂ肪זEj󂳂C̍זEЂזE}Nt@[W荞݁CזEЂɊ܂܂邪R𕪉Ryv`h𐶐D̍זE͍R񎦍זEƂ΂CMHCimajor histocompatibility complexCvgDK`q́j̃NXIq邢̓NXIIqɂĂRyv`h񎦂i<a href="#F1">}1</a>jDqg̏ꍇCMHCHLAihuman leukocyte antigenCqg^RjƂ΂ĂDL[TזEMHCNXIqɒ񎦂ꂽRyv`hTזEêɂFVOi`BƂƂɁCR񎦍זE̕\ʂɑ݂鋤h^pNƑݍp邱ƂɂCזEU銈L[TזEɂȂD

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@זE̔rƔɂƉu@\</strong>
ȍזË`qƂɂ肪זEDזEƁC͂߂ɎRƉun@\Ci`L[זEȂǂɂ肪זEj󂳂D}Nt@[W邢͎זE͔j󂳂ꂽזE̍זEЂ荞݁CR𕪉Ryv`hƂĒ񎦂D̂Ryv`hɂs^̃wp[TזE邢̓L[TזEClƉunɂ邪זE̔r@\D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.1.png&amp;caption=fig1-caption-text]

@זE͂܂܂ȖƉu@\ĈȂɂ͐䐫TזE⍜R}זEƂƉu}זẼN[gӂ܂D䐫TזE͍R񎦍זE̋h^pN̋@\ቺL[TזEsDR}זE̓TCgJC邢͍זEQ^pNYL[TזE̋@\ѐቺDRƉuSƉuזEƂ̗}SƉuזE̋@\ɂĂ͂܂sȓ_C𖾂邱ƂłʓIȂƉuÖ@̊J\ɂȂƎvD

<h2>3DƉu`FbN|Cg^pNCTLA-4</h2>
@CTLA-4icytotoxic T-lymphocyte-associated antigen 4j1987NɃ}EXɗRL[TזEN[cDNACu[`qN[jOꂽCpɓL̖ƉuOuX[p[t@~[ɑ铜^pNł<a href="#R4"><sup>4)</sup></a>D1988Nɂ̓qgɂĂ肳<a href="#R5"><sup>5)</sup></a>C1991N1992NCTLA-4-ƉuOuZ^pNpɂCTLA-4镪q@\TזE̖Ɖu}邱Ƃꂽ<a href="#R6"><sup>6,7)</sup></a>DɁCCTLA-4ƓƉuOuX[p[t@~[ɑ铜^pNłCD28肳CCTLA-4Ƃ͑Ώ̓ITזE@\Ƃ񍐂ꂽDCTLA-4CD28̋@\lCCTLA-4̋@\}CD28VOiɂTזE̊𑣐i邱Ƃ̑ޏkɂȂƕ񍐂͂߁C1996Nɂ͒S}EXւ̍RCTLA-4R̂̓^ɂᇂ̑ޏkʂώ@ꂽƂ񍐂ꂽ<a href="#R8"><sup>8)</sup></a>D̕񍐂ĈɂčRCTLA-4R̂̓^ɂƉůᇂ̑ޏk𑣐i邱ƂC͂߂Ă̗łD
@CTLA-4ƉuזE̕sCD28VOiƂ̋ɈˑDCTLA-4CD28͂ƂɁCR񎦍זE邢͂זE̕\ʂɑ݂CD80iB7-1j邢CD86iB7-2jƑݍp邱Ƃɂ@\DCD28͍PITזE̕\ʂɔĂ邪CCTLA-4TזEĂȂƂɂ͍זE̓ɑ݂ƍזE̕\ʂւƈڍsDCD28VOiɂTזE̊̂̂CCTLA-4@\邱ƂɂTזE̊͗}邪CCTLA-4CD80邢CD86Ƃ̐eaCD28CD80邢CD86Ƃ̐ea10`100{CTזE̊̂̂ɂCTLA-4DIɋ@\<a href="#R9"><sup>9)</sup></a>D̃tB[hobN@\ɂCTזẺߏȉ͗}Ăi<a href="#F2">}2</a>jD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@CTLA-4̋@\</strong>
iajTזE̊DTזE̓}Nt@[WזEMHCqɒ񎦂ꂽRyv`hTזEêɂFVOi`BDɁCCD80邢CD86CD28Ƃ̑ݍpɂCD28VOi`BCTזE͊D
ibjTזE̗}DTזE̕\ʂɂCTLA-4CCD80邢CD86ƑݍpDCD80邢CD86Ƃ̐eaCD28CTLA-4̂ق߁CCTLA-4͗DICD80邢CD86ƑݍpCTזECTLA-4VOiɂ}D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.2.png&amp;caption=fig2-caption-text]

@CTLA-4CD28CD80邢CD86Ƃ̑ݍpjQ邱ƁC܂́CCD80邢CD86זEDƂɂƉu}@\SƍlĂD҂̏ꍇĈɏqׂ鐧䐫TזEiCTLA-4PIɍזE̕\ʂɔĂj[֗^ĂCCD80邢CD86זETזE邱ƂłȂȂD̂ق̗}@\ƂẮCݍpɂCTLA-4̉̃VOiɂ钼ړIȗ}D܂ł̌ɂCCTLA-4̍זEhCɍp邢̃^pN񍐂Ă邪C}@\𒼐ڂɒS^pN͊m肳Ă炸C݂̉𖾂ɂނȂĂ<a href="#R10"><sup>10)</sup></a>D
@1996N̕񍐂ɂÂC}EXɂčRCTLA-4R̂̓^ɂᇂ̑ޏkʂ܂܂ȂɂĊmFĂ<a href="#R11"><sup>11)</sup></a>i<a href="#F3">}3</a>jD̎ʂӂ܂C2000Nɂ͂߂āCqgɂčRCTLA-4R̗̂L̕]݂C̊҂ѓ]ڐ̊҂ւ̓^ɂCFїɂĈ̍RᇖƉȗʂmFꂽ<a href="#R12"><sup>12)</sup></a>D̑IՏł͏dĂȗLQۂmFȂ߁CЂÂCIIՏёIIIՏ{ꂽDIIIՏ͐؏s\wÖ@R̈F̊676lΏۂƂCRqgCTLA-4mN[iŔiCs}ujPƁCCs}ugp100yv`hN`Ƃ̕pCgp100yv`hN`PƁC3O[vŎ{ꂽ<a href="#R13"><sup>13)</sup></a>Dgp100͈FɓٓIȎᇍRłCgpꂽyv`h̓L[TזEgp100FGsg[vz񂩂쐻ꂽDՏ̌ʁCCs}uPƁCCs}ugp100yv`hN`Ƃ̕pCgp100yv`hN`PƂ̂ꂼ̎Âɂ12J45.6C43.6C25.3C24J23.5C21.6C13.7łCCs}u̓^ɂ鉄ʂmFꂽD̗Տ̌ʂɂƂÂC2011NɃCs}u͕čFood and Drug AdministrationiFDACHiiǁj琢E̖ƉuR̈ƂďFꂽD2012Nɂ́CF̊҂ΏۂƂCs}uƃ_JoWiFɑ΂Rᇍ܁j̕p^{IIIՏ̌ʂ񍐂C_JoWPƂCs}uƂ̕pɂĉʂF߂ꂽ<a href="#R14"><sup>14)</sup></a>D݁CCs}u͂ق̈ᇂւ̌ʂ邢͂ق̕WwÖ@Ƃ̕p݂CFւ̏F̓K̊g傪i߂Ă<a href="#R15"><sup>15)</sup></a>D

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@RCTLA-4R̂ɂRᇖƉȗ</strong>
iajTזEɔCTLA-4ɑ΂RCTLA-4R̂̍pDTזEɔCTLA-4ƍRCTLA-4R̂Ƃ邱ƂɂCCTLA-4CD80邢CD86Ƃ̑ݍp͑jQCTזE̗}D
ibj䐫TזEɑ΂RCTLA-4R̂̍pD䐫TזE͍PICTLA-4𔭌ĂCCTLA-4ƌRCTLA-4R̂R̂Ɉˑ̍זEQɂ萧䐫TזEC䐫TזEɂƉu}D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.3.png&amp;caption=fig3-caption-text]

@Cs}u̓^ɂRᇖƉu͑邪CŁCƉu𑍑̓Iɑ邽߂ɎȖƉu𔭏ǂ邱Ƃ񍐂ĂDՏɂĂ̓Cs}u𓊗^҂60ɗLQۂ݂C̑畆邢͏ǂɊւ鎩ȖƉuł<a href="#R13"><sup>13)</sup></a>Dق̗ՏɂĂCs}u𓊗^҂̂񔼐l̎ȖƉu𔭏ǂƕ񍐂Ă<a href="#R14"><sup>14)</sup></a>D̂悤ȕp}邽߁CCs}u𓊗^҂ւ͖Ɖu}܂^Ă邪Cp}RᇖƉuێ̂ɍ̌KvƍlD

<h2>4DƉu`FbN|Cg^pNPD-1</h2>
@PD-1iprogrammed death 1j1992NɍזEU}EXTזEɗRcDNACu[`qN[jOꂽCƉuOuX[p[t@~[ɑ閌^pNł<a href="#R16"><sup>16)</sup></a>C1994Nɂ̓qgɂĂ肳ꂽ<a href="#R17"><sup>17)</sup></a>DCPD-1̓vOזEЂNƍlĂCKhłPD-L1iB7-H1j邢PD-L2iB7-H2jƑݍp邱ƂɂTזE̊}邱Ƃ炩ɂꂽ<a href="#R18"><sup>18)</sup></a>DPD-1TזEłȂCBזECi`L[זECi`L[TזECnזEɂĂ<a href="#R18"><sup>18)</sup></a>D܂CPD-L1͍R񎦍זEłȂCזE邢͊זEƂ܂܂ȍזEɂčPIɔĂ邪CPD-L2͍R񎦍זE邢͈ꕔBזEł̂ݍPIɔCᇂ̋ǏɂĎX̃TCgJCɂ蔭U<a href="#R19"><sup>19)</sup></a>DPD-1VOiɂTזE̗̊}@\PD-1PD-L1邢PD-L2Ƃ̑ݍpɂƂȂiDȂ킿Cݍp̂̂PD-1̍זEhCɃ`VE_yf̈łSHP-2N[gCTזEẽVOi`B^pNłZAP70s邱ƂɂTזE̋@\}<a href="#R18"><sup>18)</sup></a>D܂CPD-L1CD80Ƃ̑ݍp邱Ƃ\łČʁCTזE̊}邱Ƃ񍐂Ă<a href="#R20"><sup>20)</sup></a>D
@ᇂ̋Ǐł̓L[TזEуi`L[זEPD-1ĂCRᇖƉǔ̌ƂĂDPD-1VOiRPD-1R̂邢͍RPD-L1R̂gpđjQRᇖƉǔ}邱Ƃɂ肻̑ʂ邱Ƃ@CRPD-1R̂邢͍RPD-L1R̂pPD-1PD-L1Ƃ̑ݍpjQ邱Ƃɂ肪Ɖu𑝋ł邱Ƃ񍐂Ă<a href="#R21"><sup>21,22)</sup></a>D܂CRPD-1R̂͒Sɑ݂PD-1zCD8zTזEĊ邱Ƃ񍐂Ăi<a href="#F4">}4</a>jD

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>}4@PD-1̋@\эRPD-1R̂̍p</strong>
iajPD-1̋@\DTזE̕\ʂɔPD-1ƂזEɔPD-L1邢PD-L2Ƃ̑ݍpɂCTזEPD-1VOi}D
ibjRPD-1R̂̍pDTזEɔPD-1ƍRPD-1R̂Ƃ邱ƂɂCPD-1PD-L1邢PD-L2Ƃ̑ݍp͑jQCPD-1VOiɂTזE̗}D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.4.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.4.png&amp;caption=fig4-caption-text]

@̌ʁCRPD-1R̂邢͍RPD-L1R̂̓^ɂRᇖƉȗmFꂽƂC̍R̂p񊳎҂ΏۂƂՏJnC̗ՏʂF߂ꂽƂ̕񍐂ȂĂ<a href="#R23"><sup>23)</sup></a>DSqgR̂łRPD-1Ŕij{}uj̑IՏł́CF̊҂ɑ΂28C񏬍זEx̊҂ɑ΂18CtזE̊҂ɑ΂27̑tD̗̂Տ̌ʂC2014NɃj{}u͈F̊҂ΏۂƂÖƂē{ŏFꂽDj{}ǔʂ荂߂邽߃Cs}uƂ̕pÖ@݂ĂCF̊҂ɂāCCs}uPƂ̓^11Cj{}uPƂ̓^31̗ՏIȌʂł̂ɑ΂Cp^ł65̌ʂƂ񍐂Ă<a href="#R24"><sup>24)</sup></a>D݁Cj{}u͈F̂ق̂ΏۂƂՏ{CwÖ@Ƃ̕pÂ݂ĂCՏIȌʂ҂ĂDRPD-1R̂̓^͑Sg̖Ɖu𑝋邽߁CRCTLA-4𓊗^҂ƓlɎȖƉu𔭏ǂ銳҂mFĂCΉlKv<a href="#R24"><sup>24)</sup></a>D
@RPD-L1R̂𓊗^Տ̌ʂ2012Nɂ͂߂ĕ񍐂CŌ`̊҂ΏۂƂՏ̌ʂł́CF̊҂ɑ΂17CtזE̊҂ɑ΂12C񏬍זEx̊҂ɑ΂10C̊҂ɑ΂5̑t<a href="#R25"><sup>25)</sup></a>Ďʂ͍RPD-1R̂̒PƂł̓^̌ʂႢ̂łC̗ՏɂĎgpꂽR̂Ƃ͈قȂRPD-L1R̂pՏł́CF̊҂ɑ΂29̑tC邢́C񏬍זEx̊҂ɑ΂22CtזE̊҂ɑ΂13̑tƂ񍐂Ă<a href="#R23"><sup>23)</sup></a>D

<h2>5DƉuÖ@ɂĊ҂ق̖Ɖu`FbN|Cg^pN</h2>
@܂ŏqׂCTLA-4PD-1̂قɂƉu`FbN|Cg^pNoĂC̗Տւ̉p҂ĂD
@<strong>TIM-3</strong>iT-cell immunoglobulin and mucin containing protein-3j2002NCD4zTh1זE邢CD8zTזEɔĂ邱ƂoꂽCƉuOuX[p[t@~[ɑ閌^pNł<a href="#R26"><sup>26)</sup></a>DTIM-3̓KN`9KhƂC̑ݍpɂGtFN^[TזE̊}Dᇂ̋ǏłTIM-3݂̂邢TIM-3PD-1CD8zTזE̍RᇖƉu̎アƂqgу}EXɂĊmFĂDTIM-3VOiRTIM-3R̂ɂjQ邱ƂɂRᇖƉu𑝋ł邱Ƃ}EXɂĎ؂ĂC݁Cqgւ̉p݂Ă<a href="#R11"><sup>11)</sup></a>D
@<strong>LAG-3</strong>ilymphocyte activation gene-3j1990NCD4zTזEɂĔmFꂽCƉuOuX[p[t@~[ɑ閌^pNł<a href="#R27"><sup>27)</sup></a>D̂̌ɂCi`L[זECBזECpnזEɂĂ邱ƂoCLAG-3MHCNXIIqƂ̑ݍpɂ芈TזE}@\SDRLAG-3R̂gpLAG-3VOȋjQCсCRPD-1R̂Ƃ̕p^ɂRᇖƉu邱Ƃ}EXɂďؖĂD̎ʂRLAG-3R̂̓qgɑ΂pĂCIՏɂĈF̊҂ɑ΂铊^݂Ă<a href="#R11"><sup>11)</sup></a>D
@<strong>B7-H3</strong>C<strong>B7-H4</strong>C<strong>B7-H5</strong>iVISTAjB7t@~[ɑ閌^pNłCꂼC2001NC2003NC2011NɌoꂽ<a href="#R28"><sup>28-30)</sup></a>DB7-H3͂܂܂ȂэR񎦍זEɔĂCTזEêƑݍp邱ƂɂTזEɑ΂邢͗}̗̃VOi`BDCזEɂB7-H3̔҂̗\sǂƑւ邱ƂCᇂ̋ǏɂB7-H3VOi͍RᇖƉu}@\SƍlĂDB7-H4B7-H3ƓlɂזEэR񎦍זEɂĔĂCݍpɂ芈TזE}@\SDƂ킯Cᇂ̋Ǐł͎ᇊ֘A}Nt@[Wɂ锭ᇂ̑Ɋ֗^ĂD񊳎҂ɂB7-H4̍\sǂƑւ邱Ƃ񍐂ĂDB7-H5TזEɗ}̃VOi`B@\SC}EXł͎ᇂ̋ǏɂCD11b̔Ɛ̑ւ̂邱Ƃ񍐂ĂD܂CB7-H5VOijQ邱ƂɂRᇖƉȗ𑣐i邱Ƃ}EXɂĂ͊mFĂD3̃^pNƑݍpê͓肳ĂȂCB7-H3ɑ΂qgR̂JĂCIՏɂčĔ̂񊳎҂ɓ^Ă<a href="#R11"><sup>11)</sup></a>D
@<strong>TIGIT</strong>iT cell immunoreceptor with Ig and ITIM domainj2009NɌoꂽƉuOuX[p[t@~[ɑ閌^pNłCꂽTזEуi`L[זEɔĂ邱Ƃ񍐂Ă<a href="#R31"><sup>31)</sup></a>D̃Kh͍R񎦍זEɔĂCD112CD155łCCD226Ƃ΂êƂݍpDTIGIT邢CD226CD112邢CD155Ƃ̑ݍṕCCTLA-4邢CD28CD80邢CD86Ƃ̑ݍpƗގĂCTIGITVOi͖Ɖu}@\SCD226VOi͖Ɖu@\SDTIGITVOiCTLA-4VOiアƉu}@\CTIGITVOijQ邱ƂɂƉuł邱ƂmFĂ<a href="#R11"><sup>11)</sup></a>D

<h2>6DƉuƐ䐫TזE</h2>
@1970NɈꕔTזEƉu}@\Ƃ̕񍐂ȂC1995Nɐ䐫TזE肳Ă琢EŒڂꑽ̌i߂Ă<a href="#R32"><sup>32)</sup></a>DȂ킿CCD4zTזÊCD25zזETזEƉusS}EXik[h}EXjɈړ邱Ƃɂ莩ȖƉuǂCCD4zCD25zTזE̍Ĉړɂ肻̔ǂ}邱ƂoC䐫TזEƂCD4zCD25zTזE肳ꂽ<a href="#R32"><sup>32)</sup></a>D2001Nɂ̓qgɂĂl̐䐫TזE肳C2003Nɂ͐䐫TזẼ}X^[`qƂĒm<em>Foxp3</em>`q肳ꂽƂɂC茵ɐ䐫TזE`邱Ƃ\ɂȂ<a href="#R33"><sup>33)</sup></a>i䐫TזEɂẮC<a href="http://leading.lifesciencedb.jp/2-e005/" target="_blank">_^pEu, ̈Zr[, <strong>2</strong>, e005, 2013</a> QƂꂽjD]ʈqłFoxp3͂܂܂ȖƉu֘A`q̔𐧌䂵ĂC䐫TזEɂčPIɔĂCTLA-4̔Ɋ֗^Ă邱Ƃ炩ɂĂDCTLA-4䐫TזEɂƉu}@\ɏdvł邱Ƃ͂ɏqׂĈق̖Ɖu}@\ƂẮC}TCgJC̎Yɂ銈זE̗}CזEւ̃A|g[VX̗UȂǂĂ<a href="#R34"><sup>34)</sup></a>D
@ᇖƉuɂĐ䐫TזE͍RᇖƉu}ĂC䐫TזȄɂᇂ̑ޏkʂĂĎł́CRCD25R̂̓^ɂ鐧䐫TזȄᇂ̑ޏkɂȂ邱Ƃ؂<a href="#R35"><sup>35)</sup></a>Ĉ̃WteAőf̓^ɂFoxp3z䐫TזE̓ٓIȏľʂĂ<a href="#R36"><sup>36)</sup></a>DCTLA-4ƓlɁCPD-1LAG-3䐫TזEɔĂ邱Ƃ񍐂ĂC̖Ɖu`FbN|Cg^pNƉu}@\̉𖾂i߂Ă<a href="#R11"><sup>11)</sup></a>DƂ킯CRCTLA-4R̂ɂR̂Ɉˑ̍זEQɂ萧䐫TזEr邱ƂōRᇖƉu邱ƂdvĂDŋ߂̌ł́C䐫TזẼz[~OэזEVOiڂCCCR10ɈˑIȎᇂ̋Ǐւ̃z[~ȎjQC邢́CAZ`gXtF[[p300邢PI3Li[[̑jQɂC䐫TזE̗}@\邱ƂōRᇖƉu邱Ƃ񍐂Ă<a href="#R37"><sup>37-39)</sup></a>D
@qgł́C݂CxC̑CXC򕔂ȂǁĈɂĐ䐫TזEĂ邱Ƃ炩ɂĂ<a href="#R40"><sup>40)</sup></a>C䐫TזE̎ᇂ̋Ǐւ̐Z񊳎҂̗\sǈqł邱Ƃ񍐂ĂD̗Տf[^C䐫TזȄɂRᇖƉȗړIƂՏȂĂCqgRCD25Ŕi_NY}ujWteAőfZIL-2܂ȂǂJgpĂDCCD25͊TזEɂ锭݂邽߁CRCD25R̂̓^ɂ鐧䐫TזE̓ٓIȏ͂ĂCՏɂĂ̌ʂ͓ĂȂ<a href="#R41"><sup>41)</sup></a>D݂ł́C䐫TזEɂٓIɔ^pNWIƂ@͍ĂĈЂƂƂāCᇂ̋Ǐւ̐䐫TזE̐Z̋@\ɒڂ݂ȂĂD
@M҂́C̃Av[`ƂăPJCê̂ЂƂCCR4䐫TזE̎ᇂւ̐ZɒڂDCCR4CCL17CCL22KhƂC炪܂܂ȍזEɂᇂ̋ǏɂĕoCCR4z䐫TזEᇂ̋ǏɃN[gDCCR4z䐫TזEF̋ǏɑZĂCRCCR4R̂p邱Ƃɂ肱̐䐫TזȄ\łCɂƂȂRᇖƉu邱Ƃo<a href="#R42"><sup>42)</sup></a>D݁ČƂɁCŌ`̊҂ւ̍RCCR4R̂̓^݂ĂCᇂ̋ǏɂĐ䐫TזE邩ǂȂĂD

<h2>7DRpN`Ö@</h2>
@Ɖu`FbN|Cg^pN̑jQɂ邪ƉuÖ@́CSg̖ƉuזEٓIɑ邱ƂŎᇂ̑ޏkɂȂĂ邪C̔ʁCɂqׂ悤ɁCƉuזE̊ɂƂȂȖƉu𔭏ǂĂ܂DŁCזEٓIɍUƉuזÊ݂邪񃏃N`Ö@̊Ji߂ĂD񃏃N`Ö@ł͓̖ƉuזÊ݂邽߁CȖƉu̔ǂ}邱ƂłDN`Ɏgp邪RƂẮCRyv`hCŜRCRyv`h񎦂זEgpĂ<a href="#R43"><sup>43)</sup></a>D܂ŁĈRoĂĈȂ炪񃏃N`Ö@ɓKĂ邪RsbNAbvĂ<a href="#R44"><sup>44)</sup></a>D̕񍐂ł́CÌʁCƉuCِȂǂ̍ڂl@Ĉ̂̂RNÂĂDɂƁCWT-1ŏʂɈʒuĂCÂMUC-1ʒu邪CɏqׂCs}u̗ՏɂĎgpꂽgp10016ԖڂɈʒuĂDāC͖Ɖu`FbN|Cg^pN̑jQ܂WT-1邢MUC-1ƂRN`Ƃĕp邱ƂCʓIȂƉuÖ@ɂȂ\D

<h2>8DזEړÖ@</h2>
@1972NɎᇂ̋ǏɃpZĂ銳҂͗\ǍDł邱ƂC̕񍐂ƂɁCᇐZp邢͈`qσppזEړÖ@̊Ji߂Ă<a href="#R45"><sup>45)</sup></a>D̏ꍇCRɓٓITזEȕ@Ŕ|{đC񊳎҂̑̓ւړ邱Ƃɂ肪זE͂ɔr邱ƂړIƂĂDᇐZp̈ړÖ@ɂẮC񊳎҂ɗRᇐZp炪RɓٓIȃL[TזEoCC^[CL2݂̑̂Ƃőʔ|{̂C҂ֈړĂD̂ق̃Av[`ƂẮC񊳎҂̎悵PjזEɂRɓٓITזEê̈`q𓱓ClHIɂRɓٓIȃL[TזE쐻̂C҂ֈړ@{ĂDߔNC`qσp쐻@̂ȂŔWĂ̂CLRê𔭌TזEpÖ@łD̃LRê͂RFR̂Ƃɍ쐻ĂCȂ킿CR̂2̍RF̈Ȃe̗lhCCD3邢͋h^pN̍זEђʃhCэזEhC\ɂȂĂi<a href="#F5">}5</a>jDLRê̂Ă_́CRւ̌͂TזEêɋƁCMHCqɍR𒼐ړIɔFł邱ƂłD܂CזEђʃhC邢͍זEhC̑gς邱ƂɂCLRê𔭌TזE̐͂E͂コ邱ƂłD̍זEړÖ@͂܂܂Ȃɑ΂ՏsȂĂČʂ҂Ă<a href="#R45"><sup>45)</sup></a>D

<a name="F5"></a><div id="fig5-caption-text" style="display: none;"><strong>}5@LRê𔭌TזE̍\</strong>
זEFR̂2̍RFʂȂe̗lhCɁCCD3̍זEOhCCזEђʃhCCזEhCɌC̃LRêTזEɂĔD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.5.jpg" target="_blank">[Download]</a></div>[hs_figure id=5&amp;image=/wordpress/wp-content/uploads/2015/04/Nishikawa-5.e005-Fig.5.png&amp;caption=fig5-caption-text]


<h2></h2>
@ƉuÖ@͂܂ł̂񎡗Â傫ςLȎÖ@ƂȂD݁CƂڂĂ̂Ɖu`FbN|Cg^pNjQłC܂܂Ȍ^pNWIƂ܂̊J}ɐi߂ĂDŁCׂۑ͑ĈЂƂpłDƉu`FbN|Cg^pNjQɊւĂ͖Ɖu}̉ɂ莩ȖƉu𔭏ǂ邱ƂmFĂCזEړÖ@ɂĂ͉ߏTזEړ邱Ƃɂ艊ǐTCgJCYTCgJCXg[𐶂CȂ̍זȄQɂȂĂD̂ƉuÖ@ł͂̕pl̂͂̂ƁC҂ɂƉuÖ@IKvDłɁCRCTLA-4R̂邢͍RPD-1R̂̓^ɂᇂ̑ޏkʂ҂́CVK邢͕ψق̂RĂƂ񍐂ĂDƉuÖ@͋}ɔWĂĂC܂܂ȎÖ@JĂD̎Ö@𕹗pĂƂC悢ƉuÖ@̊JɂȂĂƊmMĂD

<h2> </h2>
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</ol>
<div class="au-profile">
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