Molecular and cellular basis of T cell lineage commitment: An overview

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  • Seminars in Immunology 22 (2010) 253

    Contents lists available at ScienceDirect

    Seminars in Immunology

    journa l homepage: www.e lsev ier .com/ locate /ysmim


    Molecular and cellular basis of T cell lineage commitment: An overview

    All multtilized cell tdistinct andthehighly ccells arise wthe capabilstep of celluplexity, incrgreater funcomplexitytal potentiawith the ennally differeof an indivspecializatidevelopme

    Cells ohematopoiespecializedinitiated byhave seen athat can bein the thymdeterminatthat stimulImmunologfrom earlyand positivfunctional e

    In this iT cell fate ais thoughtfby Pear andinterplay becuss importdevelopme

    lectiiga-Pscribt in ctionl. [6]cytesntiatctionn TCon o


    na DANotchiro-Ohent. Snte R,olecu;22:2ovic Dunol 2hamax-spe;22:2elut Rptor siunol 2yamairecti

    1044-5323/$ doi:10.1016/j.see front matter. Published by Elsevier Ltd.smim.2010.06.001icellular organisms initially develop from a single fer-hat differentiates into all different cell types, each withhighly specialized functions. Cellular development is

    omplexprocess bywhichheterogeneous populations ofith increasingly complexmolecular functions andwithity of performing increasingly specialized tasks. Everylar differentiation generates increasedmolecular com-eased specialization, and the acquisition of greater andctional abilities. However, concomitant with increased, specialization, and functional ability, the developmen-l of differentiating cells becomes increasingly limitedd result that the cells adopt a specic cell fate and termi-ntiate into a specic cell type. So from the perspectiveidual cell, development results in steadily increasingon and steadily diminishing potential for alternativental outcomes.f the immune system derive from multipotenttic stem cells that ultimately differentiate into highlyimmune cells, and they do so in response to signalsvarious environmental stimuli. The last few years

    n explosion in our knowledge of hematopoietic stemsignaled to differentiate into mature T lymphocytesus, the transcription factors that are major players inion of T cell lineage fate, and the environmental signalsate T cell differentiation. This issue of Seminars iny is focused on key steps in the development of T cellshematopoietic precursor cells, to their differentiatione selection in the thymus, to their differentiation intoffector T cells in the periphery.ssue, the mechanism by which Notch signaling elicitsnd promotes early T cell development in the thymusully considered by Bhandoola and coworkers [1] andcoworkers [2]. Taylor and coworkers describe a noveltween Notch and IL-7 signaling in the thymus and dis-ant differences betweenmurine and human thymocytent [3]. Theevolutionof in vitromodels of thymocytepos-

    itive seby Zunand deponengeneralut et athymodifferetor funbetweeentiati[7].


    [1] Sultawith

    [2] Yashopm

    [3] Viceal. M2010

    [4] DervImm

    [5] Takacorte2010

    [6] BossreceImm

    [7] Nakathe don, and what has been learned from them, is revieweducker and colleagues [4]. Takahama et al. [5] discusse the surprising discovery of a unique proteosome com-ortical thymic epithelial cells that is important for theofMHC class I selecting peptides for CD8+ T cells. Bosse-describe how sensor transcription factors in immatureare activated during positive selection to induce the

    ionof thymocytes intomatureT cellswith specic effec-s. And Nakayama and coworkers describe the interplayR and cytokine signals involved in the peripheral differ-f T helper cell subsets with different effector functions

    , Bell JJ, Zlotoff DA, DeObaldia BA, Bhandoola A. Eliciting the T cell fate. Sem Immunol 2010;22:25460.tani Y, Ohtani T, PearWS. Notch regulation of early thymocyte devel-

    em Immunol 2010;22:2619.Swainson L, Marty S, Cochonneau S, Kinet S, Zimmerman V, et

    lar and cellular basis of T cell lineage commitment. Sem Immunol705., Zuniga-Pucker JC. Positive selection of T cells, an in vitro view. Sem010;22:27686.Y, Nitta T, Ripen AM, Nitta S, Murata S, Tanaka K. Role of thymic-cic self-peptides in positive selection of T cells. Sem Immunol8793., Wang L, Xiong Y. Tenuous paths in unexplored territory: from T cellgnaling to effector gene expression during thymocyte selection. Sem010;22:294302.T, Yamashita M. The TCR-mediated signaling pathways that controlon of helper T cell differentiation. Sem Immunol 2010;22:3039.

    Alfred Singer

    Experimental Immunology Branch,National Cancer Institute, 9000 Rockville Pike,

    Bethesda, MD 20892, United States

    Tel.: +1 301 496 5461; fax: +1 301 496 0887.E-mail address: