scholarly journals Blockade of transgenic gamma delta T cell development in beta 2-microglobulin deficient mice.

1992 ◽  
Vol 11 (1) ◽  
pp. 25-31 ◽  
Author(s):  
P. Pereira ◽  
M. Zijlstra ◽  
J. McMaster ◽  
J.M. Loring ◽  
R. Jaenisch ◽  
...  
2019 ◽  
Author(s):  
Shahan Mamoor

Gamma delta T-cells are a lymphocyte subset that display gamma delta T-cell receptors rather than the alpha beta T-cell receptors that alpha beta T cells like CD4 helper and CD8 cytotoxic T-cells display, and whose function straddles the intersection of innate and adaptive immune cells (1). To understand the transcriptional behavior of gamma delta T-cells during mammalian development, we performed global differential gene expression of datasets encompassing transcriptome data from embryonic and adult gamma delta T-cells from mice (2). These analyses revealed a species of non-coding RNA termed small nucleolar RNA, or snoRNA were among the most differentially expressed genes when comparing embryonic and adult gamma delta T-cells. Moreover, these snoRNA were uniformly down-regulated over the course of gamma delta T-cell development. These data demonstrate unprecedented developmental repression of snoRNA in lymphocytes and suggest that stage-specific repression of snoRNAs may serve some vital developmental purpose in the function of gamma delta T-cells.


Nature ◽  
1994 ◽  
Vol 372 (6506) ◽  
pp. 560-563 ◽  
Author(s):  
Sharon L. Erickson ◽  
Frederic J. de Sauvage ◽  
Kristine Kikly ◽  
Karen Carver-Moore ◽  
Sharon Pitts-Meek ◽  
...  

2004 ◽  
Vol 200 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Y. Jeffrey Chiang ◽  
Connie L. Sommers ◽  
Martha S. Jordan ◽  
Hua Gu ◽  
Lawrence E. Samelson ◽  
...  

c-Cbl is an adaptor protein that negatively regulates signal transduction events involved in thymic-positive selection. To further characterize the function of c-Cbl in T cell development, we analyzed the effect of c-Cbl inactivation in mice deficient in the scaffolding molecule SLP-76. SLP-76–deficient mice show a high frequency of neonatal lethality; and in surviving mice, T cell development is blocked at the DN3 stage. Inactivation of c-cbl completely reversed the neonatal lethality seen in SLP-76–deficient mice and partially reversed the T cell development arrest in these mice. SLP-76−/− Cbl−/− mice exhibited marked expansion of polarized T helper type (Th)1 and Th2 cell peripheral CD4+ T cells, lymphoid infiltrates of parenchymal organs, and premature death. This rescue of T cell development is T cell receptor dependent because it does not occur in recombination activating gene 2−/− SLP-76−/− Cbl−/− triple knockout mice. Analysis of the signal transduction properties of SLP-76−/− Cbl−/− T cells reveals a novel SLP-76– and linker for activation of T cells–independent pathway of extracellular signal–regulated kinase activation, which is normally down-regulated by c-Cbl.


2002 ◽  
Vol 99 (14) ◽  
pp. 9398-9403 ◽  
Author(s):  
O. F. Bueno ◽  
E. B. Brandt ◽  
M. E. Rothenberg ◽  
J. D. Molkentin

1992 ◽  
Vol 89 (13) ◽  
pp. 6070-6074 ◽  
Author(s):  
M. K. Spriggs ◽  
B. H. Koller ◽  
T. Sato ◽  
P. J. Morrissey ◽  
W. C. Fanslow ◽  
...  

1992 ◽  
Vol 89 (2) ◽  
pp. 653-657 ◽  
Author(s):  
I. Correa ◽  
M. Bix ◽  
N. S. Liao ◽  
M. Zijlstra ◽  
R. Jaenisch ◽  
...  

1998 ◽  
Vol 63 (6) ◽  
pp. 669-677 ◽  
Author(s):  
Allison M. Baird ◽  
Daniel C. Thomis ◽  
Leslie J. Berg

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 73-73
Author(s):  
Kazuaki Yokoyama ◽  
Nozomi Yokoyama ◽  
Kiyoko Izawa ◽  
Ai Kotani ◽  
Ratanakanit Harnprasopwat ◽  
...  

Abstract Abstract 73 Interleukin-7 (IL7) is essential for T cell development and homeostasis. Dysregulation of signals that control normal T-cell development has been implicated in the onset of T-cell acute lymphoblastic leukemia (T-ALL). By analogy to activating mutations in the Notch pathways, we hypothesized that any mutations in the IL7 signaling axis might also contribute to T-ALL. Direct sequencing of human IL7 receptor a chain (hIL7RA) gene in a panel of 16 T-ALL cell lines identified two types of mutations in two different cell lines. One was an insertion mutation of 4 amino acids (LSRC) in the transmembrane region (INS, Fig.1A) from DND-41, a gamma-delta TCR+ T-ALL cell line, and the other was a truncated, loss-of-function, mutation in the cytoplasmic region from MOLT-4. We demonstrated that hIL7RA-INS mutant spontaneously formed a homodimer and constitutively activated downstream signals including Stat family members (1, 3 and 5), Akt and Erk via Jak1, but not Jak3. Next, we investigated oncogenic activity of hIL7RA-INS in primary hematopoietic progenitor cells. To this aim, lin− E.14 Balb/c fetal liver (FL) cells were retrovirally transduced with hIL7RA-INS in parallel with hIL7RA-wild type (WT), and then tested for their cytokine dependence in vitro. As expected, only hIL7RA-INS-transduced lin−FL cells showed abrogation of cytokine dependence. hIL7RA-transduced lin−FL cells were also transplanted into lethally irradiated syngeneic mice. Within 7–9 weeks after transplantation of lin−FL cells transduced with hIL7RA-INS, but not with hIL7RA-WT, recipient mice developed well-tolerated myelo- and lymphoproliferative disorders, characterized by marked leukocytosis, systemic lymphadenopathy and splenomegaly (Fig.1B). Notably, concomitant increase in hIL7RA+gamma-delta TCR+ T cells and decrease in B cells were observed in peripheral blood (Fig.1C). Histological examination of bone marrow, spleen and liver specimens from diseased mice revealed moderate to severe myeloid hyperplasia, disrupted splenic architecture by disseminated mature myeloid cells and infiltration of both myeloid and mononuclear cells into hepatic parenchyma, respectively. In addition, recipient mice for hIL7RA-INS-transduced lin−FL cells frequently manifested ruffled fur as well as mononuclear cell infiltration into salivary gland and pericardium, suggesting an autoimmune-like disorder. However, during median follow-up of 11 weeks, these recipient mice did not develop either overt leukemia or lymphoma, indicating that additional transforming events are required for evolution to aggressive hematological malignancies. These in vivo findings highlighted the possibility that aberrant signals via IL7RA in hematopoietic stem/progenitor cells might preferentially stimulate myelopoiesis over lymphopoiesis, and also confirmed the essential role of IL7RA in gamma-delta TCR+ T cell development, previously shown by IL7RA-knockout mice. Taken together, we speculated that dysregulated IL7RA signaling axis might be involved in the onset of T-ALL, especially with gamma-delta TCR+ phenotype. Finally, the present study, together with the recent report (JEM 208:901, 2011), emphasizes the significance of the sequential Notch-IL7RA pathways in the pathogenesis of T-ALL as well as the dominant role of the IL7RA/Jak1 axis in IL7 proliferative signal. Disclosures: No relevant conflicts of interest to declare.


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