ࡱ> 574[bjbj 4ΐΐYYYYYmmmm ym\.$,h!YcccYY>cRYYc=&Pm"{H\Yxd|z\cccc :Altered NK cell development and enhanced NK cell-mediated resistance to MCMV infection in NKG2D-deficient mice Biljana Zafirova1, Sanja Mandari1, Ronald Antulov1, Astrid Krmpoti1, Helena Jonsson2,Wayne M. Yokoyama2, Stipan Jonji1 and Bojan Poli1 1Department of Histology and Embryology, University of Rijeka School of Medicine, B. Branchetta 20, HR-51000 Rijeka, Croatia 2Howard Hughes Medical Institute, Rheumatology Division, Washington University Medical Centre, 660 S. Euclid Ave, Box 8045, St. Louis, MO 63110 U.S.A NKG2D is a potent activating receptor on NK cells which acts as a molecular sensor for stress exposed cells expressing NKG2D ligands such as infected or tumor transformed cells. Although NKG2D is expressed on NK cell precursors, its role in NK cell development is still not known. We have generated NKG2D-deficient mice by targeting the Klrk-1 locus. Here we provide evidence for dual role of NKG2D in the physiology of NK cells: one, rather regulatory, implicated in their development, homeostasis and survival, and, other, important for exerting their effector functions. We observed the following consequences of NKG2D deficiency on the NK cell development and homeostasis: a) faster division of NK cells; b) perturbation in size of NK cell subpopulations and, c) their augmented sensitivity to apoptosis. As expected, NKG2D-/- NK cells were considerably less responsive to tumor cell targets expressing NKG2D ligands, thus confirming the important role of NKG2D for exertion of their effector functions NKG2D-/- mice however showed an enhanced NK cell-mediated resistance to MCMV infection as a consequence of NK cell dysregulation. Altogether, these findings provide evidence for yet unknown regulatory function of NKG2D in NK cell physiology.  " B D f h > J w x   _ f JM U~Ź񪏋h01[hJ/ hBxhBxhe-,hBxH*he-,hBx6 he-,hBxhe-,hB.5hBxh.5mH sH hBxB*mH phsH hnA h3hBx hBxH*hBxhBxH*h4hBxH*hBx h.5 hBx50 w   ca\gd01[JEƀn`gdBxgdBxGC$EƀdžgdBxgd. gd01[21h:pt/ =!"#$% ^ 2 0@P`p2( 0@P`p 0@P`p 0@P`p 0@P`p 0@P`p 0@P`p8XV~_HmHnHsHtH@`@ .NormalCJ_HaJmH sH tH DA D Default Paragraph FontRiR 0 Table Normal4 l4a (k ( 0No List HH > Balloon TextCJOJQJ^JaJNN >Balloon Text CharCJOJQJ^JaJPK![Content_Types].xmlj0Eжr(΢Iw},-j4 wP-t#bΙ{UTU^hd}㨫)*1P' ^W0)T9<l#$yi};~@(Hu* Dנz/0ǰ $ X3aZ,D0j~3߶b~i>3\`?/[G\!-Rk.sԻ..a濭?PK!֧6 _rels/.relsj0 }Q%v/C/}(h"O = C?hv=Ʌ%[xp{۵_Pѣ<1H0ORBdJE4b$q_6LR7`0̞O,En7Lib/SeеPK!kytheme/theme/themeManager.xml M @}w7c(EbˮCAǠҟ7՛K Y, e.|,H,lxɴIsQ}#Ր ֵ+!,^$j=GW)E+& 8PK!Ptheme/theme/theme1.xmlYOo6w toc'vuر-MniP@I}úama[إ4:lЯGRX^6؊>$ !)O^rC$y@/yH*񄴽)޵߻UDb`}"qۋJחX^)I`nEp)liV[]1M<OP6r=zgbIguSebORD۫qu gZo~ٺlAplxpT0+[}`jzAV2Fi@qv֬5\|ʜ̭NleXdsjcs7f W+Ն7`g ȘJj|h(KD- dXiJ؇(x$( :;˹! I_TS 1?E??ZBΪmU/?~xY'y5g&΋/ɋ>GMGeD3Vq%'#q$8K)fw9:ĵ x}rxwr:\TZaG*y8IjbRc|XŻǿI u3KGnD1NIBs RuK>V.EL+M2#'fi ~V vl{u8zH *:(W☕ ~JTe\O*tHGHY}KNP*ݾ˦TѼ9/#A7qZ$*c?qUnwN%Oi4 =3ڗP 1Pm \\9Mؓ2aD];Yt\[x]}Wr|]g- eW )6-rCSj id DЇAΜIqbJ#x꺃 6k#ASh&ʌt(Q%p%m&]caSl=X\P1Mh9MVdDAaVB[݈fJíP|8 քAV^f Hn- "d>znNJ ة>b&2vKyϼD:,AGm\nziÙ.uχYC6OMf3or$5NHT[XF64T,ќM0E)`#5XY`פ;%1U٥m;R>QD DcpU'&LE/pm%]8firS4d 7y\`JnίI R3U~7+׸#m qBiDi*L69mY&iHE=(K&N!V.KeLDĕ{D vEꦚdeNƟe(MN9ߜR6&3(a/DUz<{ˊYȳV)9Z[4^n5!J?Q3eBoCM m<.vpIYfZY_p[=al-Y}Nc͙ŋ4vfavl'SA8|*u{-ߟ0%M07%<ҍPK! ѐ'theme/theme/_rels/themeManager.xml.relsM 0wooӺ&݈Э5 6?$Q ,.aic21h:qm@RN;d`o7gK(M&$R(.1r'JЊT8V"AȻHu}|$b{P8g/]QAsم(#L[PK-![Content_Types].xmlPK-!֧6 +_rels/.relsPK-!kytheme/theme/themeManager.xmlPK-!Ptheme/theme/theme1.xmlPK-! ѐ' theme/theme/_rels/themeManager.xml.relsPK]  \(# AA@0(  B S  ?,ܚ,ښۚٚٚlۚښlښۚlܚܚܚ,ݚlݚݚggo     mvv     ;*urn:schemas-microsoft-com:office:smarttagsaddress>*urn:schemas-microsoft-com:office:smarttags PostalCode9*urn:schemas-microsoft-com:office:smarttagsState:*urn:schemas-microsoft-com:office:smarttagsStreet=*urn:schemas-microsoft-com:office:smarttags PlaceType=*urn:schemas-microsoft-com:office:smarttags PlaceNameB *urn:schemas-microsoft-com:office:smarttagscountry-region9 *urn:schemas-microsoft-com:office:smarttagsplace8*urn:schemas-microsoft-com:office:smarttagsCity>*urn:schemas-microsoft-com:office:smarttags PersonName B  1JLNOY9Aq~\_33NBJ>wWbMjJ/01[}4dg7lBxRqdI^.nAB.o9s"x^?_tS@`xx@Unknown Bojan PolicbiljanaG* Times New Roman5Symbol3. * Arial5. *aTahomaACambria Math"1hˆˆ   a24d2qHX ?g2!xxAbstractBiljana ZafirovabiljanaOh+'0|  8 D P\dlt AbstractBiljana ZafirovaNormalbiljana2Microsoft Office Word@F#@P@P ՜.+,0 hp|     Abstract Title  !"#%&'()*+-./01236Root Entry F&P8Data  1TableWordDocument4SummaryInformation($DocumentSummaryInformation8,CompObjy  F'Microsoft Office Word 97-2003 Document MSWordDocWord.Document.89q