Development and Selection of T Cells: Facts and Puzzles

Kisielow, Paweł; H, von Boehmer

doi:10.1016/s0065-2776(08)60620-3

Cited by 415 publications

(259 citation statements)

References 588 publications

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“…Thereafter, those positively selected cells with dangerously high affinity for self-MHC/peptide ligands are also deleted by apoptosis (negative selection), and only a small fraction (3-5%) is released to the periphery to constitute the mature T cell pool (reviewed in ref. 2).…”

Section: Homeostatic T Cell Anti-self Proliferationmentioning

confidence: 99%

T cell homeostasis and systemic autoimmunity

Theofilopoulos

Dummer²,

Kono³

2001

J. Clin. Invest.

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Section: Homeostatic T Cell Anti-self Proliferationmentioning

confidence: 99%

T cell homeostasis and systemic autoimmunity

Theofilopoulos

Dummer²,

Kono³

2001

J. Clin. Invest.

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“…D uring thymic development, lymphoid precursors undergo successive phases of differentiation, expansion, and selection (1). The CD4 and CD8 double negative (DN) 3 cell subset that represents 1-5% of the total thymocytes includes mature CD3-positive cells (mostly ␥␦ T cells) as well as at least four immature thymocyte subsets that can be distinguished based on surface expression of CD44 (Pgp-1), CD25 (IL-2R␣), and CD117 (c-kit).…”

mentioning

confidence: 99%

Transgenic Expression of the p16INK4a Cyclin-Dependent Kinase Inhibitor Leads to Enhanced Apoptosis and Differentiation Arrest of CD4−CD8− Immature Thymocytes

Lagresle-Peyrou

Gardie

Eyquem

et al. 2002

The Journal of Immunology

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In the thymus, T cell development proceeds by successive steps of differentiation, expansion, and selection. Control of thymocyte proliferation is critical to insure the full function of the immune system and to prevent T cells from transformation. Deletion of the cell cycle inhibitor p16INK4a is frequently observed in human T cell neoplasias and, in mice, gene targeted inactivation of the Ink4a locus enhances thymocyte expansion and predisposes mutant animal to tumorigenesis. Here, we investigate the mechanism by which p16Ink4a controls thymocyte development by analyzing transgenic mice expressing the human p16INK4a into the T cell lineage. We show that forced expression of p16INK4a in thymocytes blocked T cell differentiation at the early CD4−CD8−CD3−CD25+ stage without significantly affecting the development of γδ T cells. Pre-TCR function was mimicked by the induction of CD3 signaling in thymocytes of recombinase activating gene (RAG)-2-deficient mice (RAG-2−/−). Upon anti-CD3ε treatment in vivo, p16INK4a-expressing RAG-2−/− thymocytes were not rescued from apoptosis, nor could they differentiate. Our data demonstrate that expression of p16INK4a prevents the pre-TCR-mediated expansion and/or survival of differentiating thymocytes.

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“…In the mouse, these cell subsets, delineated via cell-surface expression of discrete molecular markers, are commonly named DN1-3 cells, with DN2 and DN3 displaying predominant DJb-and VDJb-rearranged products, respectively. Allelic exclusion/feedback inhibition is tightly coupled to b-selection prior to the DN3-DN4 stage transition, with cells not passing this checkpoint doomed to apoptosis or, possibly, diverted toward a distinct gdT cell lineage (31). Heterogeneity in DN1-3 cell distribution, despite evidence of cycled seeding by T cell precursors (26), suggests an uncoordinated mode of activation and course of DN cell differentiation and/or recombination programs.…”

Section: Formulation Of the Model: Basic Featuresmentioning

confidence: 99%