Transmission tunneling through the periodic sequence of double-negative and double-positive layers

Studies have suggested that antigen receptor loci adopt contracted conformations to promote long-distance interactions between gene segments during V(D)J recombination. The Tcra/Tcrd locus is unique because it undergoes highly divergent Tcrd and Tcra recombination programs in CD4−CD8− double negative (DN) and CD4+CD8+ double positive (DP) thymocytes, respectively. Using three-dimensional fluorescence in situ hybridization, we asked whether these divergent recombination programs are supported by distinct conformational states of the Tcra/Tcrd locus. We found that the 3′ portion of the locus is contracted in DN and DP thymocytes but not in B cells. Remarkably, the 5′ portion of the locus is contracted in DN thymocytes but is decontracted in DP thymocytes. We propose that the fully contracted conformation in DN thymocytes allows Tcrd rearrangements involving Vδ gene segments distributed over 1 Mb, whereas the unique 3′-contracted, 5′-decontracted conformation in DP thymocytes biases initial Tcra rearrangements to the most 3′ of the available Vα gene segments. This would maintain a large pool of distal 5′ Vα gene segments for subsequent rounds of recombination. Thus, distinct contracted conformations of the Tcra/Tcrd locus may facilitate a transition from a Tcrd to a Tcra mode of recombination during thymocyte development.

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Lateral shift of acoustic wave at interface between double-positive and double-negative media

Physics Letters A ◽

10.1016/j.physleta.2006.05.065 ◽

2006 ◽

Vol 358 (5-6) ◽

pp. 484-486 ◽

Cited By ~ 6

Author(s):

Lunwu Zeng ◽

Runxia Song

Keyword(s):

Acoustic Wave ◽

Lateral Shift ◽

Double Negative ◽

Double Positive

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Defined αβ T Cell Receptors with Distinct Ligand Specificities Do Not Require Those Ligands to Signal Double Negative Thymocyte Differentiation

Journal of Experimental Medicine ◽

10.1084/jem.20032204 ◽

2004 ◽

Vol 199 (12) ◽

pp. 1719-1724 ◽

Cited By ~ 8

Author(s):

Batu Erman ◽

Terry I. Guinter ◽

Alfred Singer

Keyword(s):

T Cell ◽

T Cell Development ◽

Cell Receptor ◽

Peptide Ligands ◽

Double Negative ◽

Antigen Receptors ◽

Double Positive ◽

Recombination Activating Gene ◽

Thymocyte Differentiation ◽

Deficient Mice

During T cell development in the thymus, pre–T cell receptor (TCR) complexes signal CD4− CD8− (double negative [DN]) thymocytes to differentiate into CD4+ CD8+ (double positive [DP]) thymocytes, and they generate such signals without apparent ligand engagements. Although ligand-independent signaling is unusual and might be unique to the pre-TCR, it is possible that other TCR complexes such as αβ TCR or αγ TCR might also be able to signal the DN to DP transition in the absence of ligand engagement if they were expressed on DN thymocytes. Although αγ TCR complexes efficiently signal DN thymocyte differentiation, it is not yet certain if αβ TCR complexes are also capable of signaling DN thymocyte differentiation, nor is it certain if such signaling is dependent upon ligand engagement. This study has addressed these questions by expressing defined αβ TCR transgenes in recombination activating gene 2−/− pre-Tα−/− double deficient mice. In such double deficient mice, the only antigen receptors that can be expressed are those encoded by the αβ TCR transgenes. In this way, this study definitively demonstrates that αβ TCR can in fact signal the DN to DP transition. In addition, this study demonstrates that transgenic αβ TCRs signal the DN to DP transition even in the absence of their specific MHC–peptide ligands.

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A novel single step double positive double negative selection strategy for β-globin gene replacement

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2006.04.060 ◽

2006 ◽

Vol 345 (1) ◽

pp. 14-20 ◽

Cited By ~ 2

Author(s):

H. Khanahmad ◽

M.R. Noori Daloii ◽

M.A. Shokrgozar ◽

K. Azadmanesh ◽

A.R. Niavarani ◽

...

Keyword(s):

Negative Selection ◽

Globin Gene ◽

Gene Replacement ◽

Single Step ◽

Selection Strategy ◽

Double Negative ◽

Double Positive

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Immunophenotypic diversity and prognosis of adult T-cell leukemia/lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17565 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17565-17565

Author(s):

A. Carrasco ◽

B. Beltran ◽

J. Malaga ◽

G. Ferrel ◽

H. Rios ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Cell Leukaemia ◽

Final Conclusion ◽

Type I ◽

Acute Type ◽

Double Negative ◽

Double Positive ◽

Atll Patient ◽

Human T Cell

17565 Background: Adult T-cell leukaemia/lymphoma (ATLL) is an aggressive disease associated with human T-cell lymphotropic virus type-I (HTLV-I) with heterogeneous clinical presentation and outcomes, described in Southern Japan, Europe, Caribbean and previously on Pacific coast of South America including Peru (EHA 2001, abst. 304). Shimoyama’s ATLL classification (BHJ 1991:79), includes four types: acute, lymphomatous, chronic and smouldering; recently a new clinical cutaneous type had been described (BJD 2005:152). Methods: We described our experienced previously (ASH 2005, abst. 4797). Herein we analyzed immunophenotypically our ATLL patient population by flow cytometry looking for aberrant phenotypes and their correlation with overall survival. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: From July 1997 to March 2005 our registry had 69 cases, 37 had flow pre-treatment: acute type (n = 31) and lymphomatous (n = 6). Over our 37 flow done we were able to analysis only 33. The incidence of the typical (CD4+/CD8-) phenotype, the double-negative (CD4-/CD8-), the double-positive (CD4+/CD8+), and the CD8 positive (CD4-/CD8+) phenotypes was 58%, 12%, 15%, and 12% respectively. The median overall survival (OS) for the 33 patients was 4.1 months (range: 0.5–46.1). The patients with typical phenotypes had a median OS of 4.1 months better than the patients with the double-negative phenotype whom median OS was 2.0 (range: 1.5–9.7) but not significant. Median OS in the double positive and the CD4-/CD8+ phenotype population were 15.2 and 4.8 months respectively with no significance Conclusions: ATLL has a diversity of immunophenotype, our data suggest that there is not any correlation with survival, major accrual will gave us a final conclusion. No significant financial relationships to disclose.

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The transcription factor Gli3 regulates differentiation of fetal CD4–CD8– double-negative thymocytes

Blood ◽

10.1182/blood-2005-03-0998 ◽

2005 ◽

Vol 106 (4) ◽

pp. 1296-1304 ◽

Cited By ~ 32

Author(s):

Ariadne L. Hager-Theodorides ◽

Johannes T. Dessens ◽

Susan V. Outram ◽

Tessa Crompton

Keyword(s):

Transcription Factor ◽

T Cell ◽

T Cell Receptor ◽

Cell Receptor ◽

T Cell Differentiation ◽

Double Negative ◽

Thymocyte Development ◽

Tcr Signaling ◽

Double Positive ◽

Dose Dependent

AbstractGlioblastoma 3 (Gli3) is a transcription factor involved in patterning and oncogenesis. Here, we demonstrate a role for Gli3 in thymocyte development. Gli3 is differentially expressed in fetal CD4–CD8– double-negative (DN) thymocytes and is most highly expressed at the CD44+ CD25– DN (DN1) and CD44–CD25– (DN4) stages of development but was not detected in adult thymocytes. Analysis of null mutants showed that Gli3 is involved at the transitions from DN1 to CD44+ CD25+ DN (DN2) cell and from DN to CD4+CD8+ double-positive (DP) cell. Gli3 is required for differentiation from DN to DP thymocyte, after pre–T-cell receptor (TCR) signaling but is not necessary for pre-TCR–induced proliferation or survival. The effect of Gli3 was dose dependent, suggesting its direct involvement in the transcriptional regulation of genes controlling T-cell differentiation during fetal development.

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