Ly49D-Mediated ITAM Signaling in Immature Thymocytes Impairs Development by Bypassing the Pre-TCR Checkpoint

A portion of the human cellular homolog of v-rel, the transforming gene of the leukemogenic retrovirus reticuloendotheliosis virus, strain T, was used to survey RNAs from several mouse tissues, selected lymphocyte populations, and hematopoietic cell lines for c-rel expression. Relatively high levels of a high-molecular-weight transcript were observed in peripheral B and T cells, whereas lower levels were detectable in functionally immature thymocytes. These results suggested that, unlike c-myb and c-ets, the c-rel proto-oncogene plays a role in later stages of lymphocyte differentiation.

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Mature and Immature Thymocytes

Progress in Immunology ◽

10.1016/b978-0-12-174685-8.50014-7 ◽

1986 ◽

pp. 95-104 ◽

Cited By ~ 2

Author(s):

Ken Shortman ◽

Roland Scollay ◽

Anne Wilson ◽

Wei-Feng Chen ◽

Tania Ewing

Keyword(s):

Immature Thymocytes

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Differential Chemotactic Behavior of Developing T Cells in Response to Thymic Chemokines

Blood ◽

10.1182/blood.v91.12.4434 ◽

1998 ◽

Vol 91 (12) ◽

pp. 4434-4443 ◽

Cited By ~ 124

Author(s):

Chang H. Kim ◽

Louis M. Pelus ◽

John R. White ◽

Hal E. Broxmeyer

Keyword(s):

T Cells ◽

Triple Negative ◽

Selection Process ◽

Chemotactic Activity ◽

Double Positive ◽

Single Positive ◽

And Migration ◽

Late Stages ◽

Immature Thymocytes ◽

Chemotactic Behavior

Abstract Differentiation-dependent thymocyte migration in the thymus may be important for T lymphopoiesis and might be regulated by thymic chemoattractants. We examined modulation of chemotactic responsiveness of thymocyte subsets during their early to late stages of development in response to 2 thymus-expressed chemokines, SDF-1 and CKβ-11/MIP-3β/ELC. SDF-1 shows chemotactic preference for immature thymocytes (subsets of triple negative thymocytes and double positive [DP] subset) over mature single positive (SP) thymocytes. CKβ-11/MIP-3β/ELC shows low chemotactic activity on the immature thymocytes, but it strongly attracts mature SP thymocytes, effects opposite to that of SDF-1. SDF-1–dependent chemoattraction of immature thymocytes is not significantly desensitized by a negative concentration gradient of CKβ-11/MIP-3β/ELC, and chemoattraction of mature SP thymocytes to CKβ-11/MIP-3β/ELC is not antagonized by SDF-1, demonstrating that these two chemokines have different chemoattractant preferences for thymocyte subsets and would probably not inhibit each other's chemotaxis in the event of microenvironmental coexpression. The chemotactic responsiveness of thymocytes and mature T cells to the 2 chemokines is respectively enhanced after selection process and migration to the spleen. These studies demonstrate the presence of thymocyte chemoattractants with differential chemotactic preference for thymocytes, a possible mechanism for thymocyte migration in the thymus.

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Developmentally regulated expression of CD3 components independent of clonotypic T cell antigen receptor complexes on immature thymocytes.

Journal of Experimental Medicine ◽

10.1084/jem.180.4.1375 ◽

1994 ◽

Vol 180 (4) ◽

pp. 1375-1382 ◽

Cited By ~ 42

Author(s):

D L Wiest ◽

K P Kearse ◽

E W Shores ◽

A Singer

Keyword(s):

T Cells ◽

T Cell ◽

Biochemical Characterization ◽

Severe Combined Immunodeficiency ◽

Structural Basis ◽

Thymocyte Development ◽

Antibody Treatment ◽

Receptor Complexes ◽

Stage Of Development ◽

Immature Thymocytes

CD3 signal transducing proteins are thought to be expressed on the surface of T cells only as part of clonotypic T cell receptor (TCR) complexes. Contrary to this paradigm, the present study describes surface expression of CD3 proteins independently of clonotypic TCR complexes, but only on immature thymocytes. Such novel clonotype-independent CD3 (CIC) complexes are composed primarily of CD3 gamma epsilon and secondarily of CD3 delta epsilon heterodimers that are independent of one another and are expressed on the cell surface in association with an unknown 90-100 kD protein termed CD3-associated protein (CD3AP). CIC complexes are expressed in normal mice on early thymocytes through the CD4+CD8+ stage of development, but not on mature peripheral T cells. Furthermore, CIC complexes are expressed by both TCR- severe combined immunodeficiency (SCID) thymocytes and thymoma cell lines, in the absence of any clonotypic chains. The isolation and biochemical characterization of surface CIC complexes provides a structural basis for the signaling effects of anti-CD3 epsilon antibody treatment in early thymocyte development.

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Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27kip1

Blood ◽

10.1182/blood.v98.5.1524 ◽

2001 ◽

Vol 98 (5) ◽

pp. 1524-1531 ◽

Cited By ~ 115

Author(s):

Joao T. Barata ◽

Angelo A. Cardoso ◽

Lee M. Nadler ◽

Vassiliki A. Boussiotis

Keyword(s):

Cell Cycle ◽

T Cell ◽

Cell Cycle Progression ◽

Lymphoblastic Leukemia ◽

Cyclin Dependent Kinase ◽

Malignant Cells ◽

Cycle Progression ◽

Interleukin 7 ◽

Cell Acute Lymphoblastic Leukemia ◽

Immature Thymocytes

In normal T-cell development interleukin-7 (IL-7) functions as an antiapoptotic factor by regulating bcl-2 expression in immature thymocytes and mature T cells. Similar to what occurs in normal immature thymocytes, prevention of spontaneous apoptosis by IL-7 in precursor T-cell acute lymphoblastic leukemia (T-ALL) cells correlates with up-regulation of bcl-2. IL-7 is also implicated in leukemogenesis because IL-7 transgenic mice develop lymphoid malignancies, suggesting that IL-7 may regulate the generation and expansion of malignant cells. This study shows that in the presence of IL-7, T-ALL cells not only up-regulated bcl-2 expression and escaped apoptosis but also progressed in the cell cycle, resulting in sequential induction of cyclin D2 and cyclin A. Down-regulation of p27kip1 was mandatory for IL-7–mediated cell cycle progression and temporally coincided with activation of cyclin-dependent kinase (cdk)4 and cdk2 and hyperphosphorylation of Rb. Strikingly, forced expression of p27kip1 in T-ALL cells not only prevented cell cycle progression but also reversed IL-7–mediated up-regulation of bcl-2 and promotion of viability. These results show for the first time that a causative link between IL-7–mediated proliferation and p27kip1 down-regulation exists in malignant T cells. Moreover, these results suggest that p27kip1 may function as a tumor suppressor gene not only because it is a negative regulator of cell cycle progression but also because it is associated with induction of apoptosis of primary malignant cells.

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