scholarly journals Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice.

1994 ◽  
Vol 180 (5) ◽  
pp. 1955-1960 ◽  
Author(s):  
J J Peschon ◽  
P J Morrissey ◽  
K H Grabstein ◽  
F J Ramsdell ◽  
E Maraskovsky ◽  
...  
Keyword(s):  
T Cell ◽  
Developmental Stages ◽  
Receptor Gene ◽  
Critical Role ◽  
Cell Receptor ◽  
High Affinity ◽  
Interleukin 7 ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Deficient Mice

Interleukin 7 (IL-7) stimulates the proliferation of B cell progenitors, thymocytes, and mature T cells through an interaction with a high affinity receptor (IL-7R) belonging to the hematopoietin receptor superfamily. We have further addressed the role of IL-7 and its receptor during B and T cell development by generating mice genetically deficient in IL-7R. Mutant mice display a profound reduction in thymic and peripheral lymphoid cellularity. Analyses of lymphoid progenitor populations in IL-7R-deficient mice define precisely those developmental stages affected by the mutation and reveal a critical role for IL-7R during early lymphoid development. Significantly, these studies indicate that the phase of thymocyte expansion occurring before the onset of T cell receptor gene rearrangement is critically dependent upon, and mediated by the high affinity receptor for IL-7.

A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor α chain-deficient mice

1997 ◽  
Vol 27 (1) ◽  
pp. 100-104 ◽  
Author(s):  
Tessa Crompton ◽  
Susan V. Outram ◽  
Jennifer Buckland ◽  
Michael J. Owen
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Interleukin 7 ◽  
Α Chain ◽  
Thymocyte Differentiation ◽  
Deficient Mice

scholarly journals Pim1 Reconstitutes Thymus Cellularity in Interleukin 7–And Common γ Chain–Mutant Mice and Permits Thymocyte Maturation in Rag- but Not Cd3γ-Deficient Mice

1999 ◽  
Vol 190 (8) ◽  
pp. 1059-1068 ◽  
Author(s):  
Heinz Jacobs ◽  
Paul Krimpenfort ◽  
Mariëlle Haks ◽  
John Allen ◽  
Bianca Blom ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Leukemia Virus ◽  
T Cell Development ◽  
Cell Receptor ◽  
Cell Development ◽  
Interleukin 7 ◽  
Tcr Signal Transduction ◽  
Slow Expansion ◽  
Deficient Mice

The majority of lymphomas induced in Rag-deficient mice by Moloney murine leukemia virus (MoMuLV) infection express the CD4 and/or CD8 markers, indicating that proviral insertions cause activation of genes affecting the development from CD4−8− pro-T cells into CD4+8+ pre-T cells. Similar to MoMuLV wild-type tumors, 50% of CD4+8+ Rag-deficient tumors carry a provirus near the Pim1 protooncogene. To study the function of PIM proteins in T cell development in a more controlled setting, a Pim1 transgene was crossed into mice deficient in either cytokine or T cell receptor (TCR) signal transduction pathways. Pim1 reconstitutes thymic cellularity in interleukin (IL)-7– and common γ chain–deficient mice. In Pim1-transgenic Rag-deficient mice but notably not in CD3γ-deficient mice, we observed slow expansion of the CD4+8+ thymic compartment to almost normal size. Based on these results, we propose that PIM1 functions as an efficient effector of the IL-7 pathway, thereby enabling Rag-deficient pro-T cells to bypass the pre-TCR–controlled checkpoint in T cell development.

scholarly journals Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria

2011 ◽  
Vol 208 (11) ◽  
pp. 2225-2236 ◽  
Author(s):  
Adeline Porcherie ◽  
Cedric Mathieu ◽  
Roger Peronet ◽  
Elke Schneider ◽  
Julien Claver ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Critical Role ◽  
Experimental Cerebral Malaria ◽  
Effector Cells ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
The Brain ◽  
Malaria Severity

The role of the IgE–FcεRI complex in malaria severity in Plasmodium falciparum–hosting patients is unknown. We demonstrate that mice genetically deficient for the high-affinity receptor for IgE (FcεRIα-KO) or for IgE (IgE-KO) are less susceptible to experimental cerebral malaria (ECM) after infection with Plasmodium berghei (PbANKA). Mast cells and basophils, which are the classical IgE-expressing effector cells, are not involved in disease as mast cell–deficient and basophil-depleted mice developed a disease similar to wild-type mice. However, we show the emergence of an FcεRI+ neutrophil population, which is not observed in mice hosting a non–ECM-inducing PbNK65 parasite strain. Depletion of this FcεRI+ neutrophil population prevents ECM, whereas transfer of this population into FcεRIα-KO mice restores ECM susceptibility. FcεRI+ neutrophils preferentially home to the brain and induce elevated levels of proinflammatory cytokines. These data define a new pathogenic mechanism of ECM and implicate an FcεRI-expressing neutrophil subpopulation in malaria disease severity.

scholarly journals The V–J Recombination of  T Cell Receptor-γ Genes Is Blocked in Interleukin-7 Receptor–deficient Mice

1996 ◽  
Vol 184 (6) ◽  
pp. 2423-2428 ◽  
Author(s):  
Kazushige Maki ◽  
Shinji Sunaga ◽  
Koichi Ikuta
Keyword(s):  
T Cell ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Mutant Mice ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Pcr Analysis ◽  
Interleukin 7 ◽  
Rag 1 ◽  
Specific Regulation ◽  
Deficient Mice

IL-7R-deficient mice have severely impaired expansion of early lymphocytes and lack γδ T cells. To elucidate the role of IL-7R on γδ T cell development, we analyzed the rearrangements of TCR-α, β, γ, and δ genes in the thymus of the IL-7R-deficient mice. Southern blot analysis with a Jγ1 probe revealed that more than 70% of Jγ1 and Jγ2 alleles are recombined to form distinct Vγ1.2–Jγ2 and Vγ2–Jγ1 fragments in control mice. On the contrary, no such recombination was detected in the mutant mice. The rearrangements in the TCR-α, β, and δ loci were comparably observed in control and mutant mice. PCR analysis indicated that the V–J recombination of all the Vγ genes is severely hampered in the mutant mice. The mRNA of RAG-1, RAG-2, Ku-80, and terminal deoxynucleotidyl transferase (TdT) genes was equally detected between control and mutant thymi, suggesting that the expression of common recombination machinery is not affected. These data demonstrated that the V–J recombination of the TCR γ genes is specifically blocked in the IL-7R-deficient mice and suggested the presence of highly specific regulation for TCR γ gene rearrangement.

scholarly journals T cell-specific deletion of Pgam1 reveals a critical role for glycolysis in T cell responses

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Koji Toriyama ◽  
Makoto Kuwahara ◽  
Hiroshi Kondoh ◽  
Takumi Mikawa ◽  
Nobuaki Takemori ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Critical Role ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Cell Proliferation And Differentiation ◽  
Tcr Signals ◽  
Deficient Mice

AbstractAlthough the important roles of glycolysis in T cells have been demonstrated, the regulatory mechanism of glycolysis in activated T cells has not been fully elucidated. Furthermore, the influences of glycolytic failure on the T cell-dependent immune response in vivo remain unclear. We therefore assessed the role of glycolysis in the T cell-dependent immune response using T cell-specific Pgam1-deficient mice. Both CD8 and CD4 T cell-dependent immune responses were attenuated by Pgam1 deficiency. The helper T cell-dependent inflammation was ameliorated in Pgam1-deficient mice. Glycolysis augments the activation of mTOR complex 1 (mTORC1) and the T-cell receptor (TCR) signals. Glutamine acts as a metabolic hub in activated T cells, since the TCR-dependent increase in intracellular glutamine is required to augment glycolysis, increase mTORC1 activity and augment TCR signals. These findings suggest that mTORC1, glycolysis and glutamine affect each other and cooperate to induce T cell proliferation and differentiation.

Linkage between atopy and the IgE high-affinity receptor gene at 11q13 in atopic dermatitis families

1998 ◽  
Vol 102 (2) ◽  
pp. 236-239 ◽  
Author(s):  
R. Fölster-Holst ◽  
Hans W. Moises ◽  
L. Yang ◽  
Wolfgang Fritsch ◽  
Jean Weissenbach ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Receptor Gene ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor

scholarly journals Novel CD28-Responsive Enhancer Activated by CREB/ATF and AP-1 Families in the Human Interleukin-2 Receptor α-Chain Locus

2001 ◽  
Vol 21 (14) ◽  
pp. 4515-4527 ◽  
Author(s):  
Jung-Hua Yeh ◽  
Patrick Lecine ◽  
Jacques A. Nunes ◽  
Salvatore Spicuglia ◽  
Pierre Ferrier ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Interleukin 2 ◽  
Cell Immune Response ◽  
High Affinity ◽  
Cd28 Costimulation ◽  
High Affinity Receptor ◽  
Reporter Assays ◽  
Affinity Receptor ◽  
Α Chain

ABSTRACT The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) critically regulates the T-cell immune response, and the α chain CD25/IL-2Rα is required for the formation of the high-affinity receptor. Tissue-specific, inducible expression of the IL-2Rα gene is regulated by at least three positive regulatory regions (PRRI, PRRII, and PRRIII), but none responded to CD28 engagement in gene reporter assays although CD28 costimulation strongly amplifies IL-2Rα gene transcription. By DNase I hypersensitivity analysis, we have identified a novel TCR-CD3- and CD28-responsive enhancer (CD28rE) located 8.5 kb 5′ of the IL-2Rα gene. PRRIV/CD28rE contains a functional CRE/TRE element required for CD28 signaling. The T-cell-specific, CD28-responsive expression of the IL-2Rα gene appears controlled through PRRIV/CD28rE by cooperation of CREB/ATF and AP-1 family transcription factors.

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