000			nab a22 7a 4500
999			_c15954 _d15954
003			PC15954
005			20210625062816.0
008			200529b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_91880 _aCriado Carrasco, Gabriel _eInstituto de Investigación i+12
245	0	0	_aCharacteristics of TCR/CD3 complex CD3{varepsilon} chains of regulatory CD4+ T (Treg) lymphocytes: role in Treg differentiation in vitro and impact on Treg in vivo. _h[artículo]
260			_bJournal of leukocyte biology, _c2014
300			_a95(3):441-50.
500			_aFormato Vancouver: Rojo JM, Ojeda G, Acosta YY, Montes-Casado M, Criado G, Portolés P. Characteristics of TCR/CD3 complex CD3{varepsilon} chains of regulatory CD4+ T (Treg) lymphocytes: role in Treg differentiation in vitro and impact on Treg in vivo. J Leukoc Biol. 2014 Mar;95(3):441-50.
501			_aPMID: 24212096
504			_aContiene 85 referencias
520			_aTregs are anergic CD4(+)CD25(+)Foxp3(+) T lymphocytes exerting active suppression to control immune and autoimmune responses. However, the factors in TCR recognition underlying Treg differentiation are unclear. Based on our previous data, we hypothesized that Treg TCR/CD3 antigen receptor complexes might differ from those of CD4(+)CD25(-) Tconv. Expression levels of TCR/CD3, CD3ε,ζ chains, or other molecules involved in antigen signaling and the characteristics of CD3ε chains were analyzed in thymus or spleen Treg cells from normal mice. Tregs had quantitative and qualitatively distinct TCR/CD3 complexes and CD3ε chains. They expressed significantly lower levels of the TCR/CD3 antigen receptor, CD3ε chains, TCR-ζ chain, or the CD4 coreceptor than Tconv. Levels of kinases, adaptor molecules involved in TCR signaling, and early downstream activation pathways were also lower in Tregs than in Tconv. Furthermore, TCR/CD3 complexes in Tregs were enriched in CD3ε chains conserving their N-terminal, negatively charged amino acid residues; this trait is linked to a higher activation threshold. Transfection of mutant CD3ε chains lacking these residues inhibited the differentiation of mature CD4(+)Foxp3(-) T lymphocytes into CD4(+)Foxp3(+) Tregs, and differences in CD3ε chain recognition by antibodies could be used to enrich for Tregs in vivo. Our results show quantitative and qualitative differences in the TCR/CD3 complex, supporting the hyporesponsive phenotype of Tregs concerning TCR/CD3 signals. These differences might reconcile avidity and flexible threshold models of Treg differentiation and be used to implement therapeutic approaches involving Treg manipulation.
710			_9625 _aInstituto de Investigación imas12
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc15954.pdf _ySolicitar documento
942			_2ddc _cART _n0