scholarly journals The Common Cytokine Receptor γ Chain Plays an Essential Role in Regulating Lymphoid Homeostasis

1997 ◽  
Vol 185 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Hiroshi Nakajima ◽  
Elizabeth W. Shores ◽  
Masayuki Noguchi ◽  
Warren J. Leonard
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Proliferation ◽  
Cell Receptor ◽  
Cytokine Receptor ◽  
Proliferating Cells ◽  
Lymphoid Development ◽  
Age Dependent ◽  
The Common ◽  
Deficient Mice

In the immune system, there is a careful regulation not only of lymphoid development and proliferation, but also of the fate of activated and proliferating cells. Although the manner in which these diverse events are coordinated is incompletely understood, cytokines are known to play major roles. Whereas IL-7 is essential for lymphoid development, IL-2 and IL-4 are vital for lymphocyte proliferation. The receptors for each of these cytokines contain the common cytokine receptor γ chain (γc), and it was previously shown that γc-deficient mice exhibit severely compromised development and responsiveness to IL-2, IL-4, and IL-7. Nevertheless, these mice exhibit an age-dependent accumulation of splenic CD4+ T cells, the majority of which have a phenotype typical of memory/activated cells. When γc-deficient mice were mated to DO11.10 T cell receptor (TCR) transgenic mice, only the T cells bearing endogenous TCRs had this phenotype, suggesting that its acquisition was TCR dependent. Not only do the CD4+ T cells from γc-deficient mice exhibit an activated phenotype and greatly enhanced incorporation of bromodeoxyuridine but, consistent with the lack of γc-dependent survival signals, they also exhibit an augmented rate of apoptosis. However, because the CD4+ T cells accumulate, it is clear that the rate of proliferation exceeds the rate of cell death. Thus, surprisingly, although γc-independent signals are sufficient to mediate expansion of CD4+ T cells in these mice, γc-dependent signals are required to regulate the fate of activated CD4+ T cells, underscoring the importance of γc-dependent signals in controlling lymphoid homeostasis.

Colitis in mice lacking the common cytokine receptor γ chain is mediated by IL-6-producing CD4+ T cells

2005 ◽  
Vol 128 (4) ◽  
pp. 922-934 ◽  
Author(s):  
Yasuyuki Kai ◽  
Ichiro Takahashi ◽  
Hiromichi Ishikawa ◽  
Takachika Hiroi ◽  
Tsunekazu Mizushima ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Receptor ◽  
The Common

scholarly journals Comprehensive Transcriptomic Comparison between Porcine CD8− and CD8+ Gamma Delta T Cells Revealed Distinct Immune Phenotype

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2165
Author(s):  
Sangwook Kim ◽  
Byeonghwi Lim ◽  
Sameer-ul-Salam Mattoo ◽  
Eun-Young Oh ◽  
Chang-Gi Jeong ◽  
...  
Keyword(s):  
T Cells ◽  
Signaling Pathway ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Cytokine Receptor ◽  
Receptor Interaction ◽  
Sequencing Analysis ◽  
Gamma Delta ◽  
Tcr Signaling ◽  
The Common

We aimed to comprehensively understand the functional mechanisms of immunity, especially of the CD8+/− subsets of gamma delta (γδ) T cells, using an RNA-sequencing analysis. Herein, γδ T cells were obtained from bronchial lymph node tissues of 38-day-old (after weaning 10-day: D10) and 56-day-old (after weaning 28-day: D28) weaned pigs and sorted into CD8+ and CD8− groups. Differentially expressed genes (DEGs) were identified based on the CD8 groups at D10 and D28 time points. We confirmed 1699 DEGs between D10 CD8+ versus D10 CD8− groups and 1784 DEGs between D28 CD8+ versus D28 CD8− groups; 646 upregulated and 561 downregulated DEGs were common. The common upregulated DEGs were enriched in the cytokine–cytokine receptor interaction and T cell receptor (TCR) signaling pathway, and the common downregulated DEGs were enriched in the B cell receptor signaling pathway. Further, chemokine-related genes, interferon gamma, and CD40 ligand were involved in the cytokine–cytokine receptor interaction and TCR signaling pathway, which are associated with inter-regulation in immunity. We expect our results to form the basic data required for understanding the mechanisms of γδ T cells in pigs; however, further studies are required in order to reveal the dynamic changes in γδ T cells under pathogenic infections, such as those by viruses.

scholarly journals Thymus-specific serine protease contributes to the diversification of the functional endogenous CD4 T cell receptor repertoire

2010 ◽  
Vol 208 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Christophe Viret ◽  
Camille Lamare ◽  
Martine Guiraud ◽  
Nicolas Fazilleau ◽  
Agathe Bour ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Serine Protease ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Tcr Repertoire ◽  
Deficient Mice

Thymus-specific serine protease (TSSP) is a novel protease that may contribute to the generation of the peptide repertoire presented by MHC class II molecules in the thymus. Although TSSP deficiency has no quantitative impact on the development of CD4 T cells expressing a polyclonal T cell receptor (TCR) repertoire, the development of CD4 T cells expressing the OTII and Marilyn transgenic TCRs is impaired in TSSP-deficient mice. In this study, we assess the role of TSSP in shaping the functional endogenous polyclonal CD4 T cell repertoire by analyzing the response of TSSP-deficient mice to several protein antigens (Ags). Although TSSP-deficient mice responded normally to most of the Ags tested, they responded poorly to hen egg lysozyme (HEL). The impaired CD4 T cell response of TSSP-deficient mice to HEL correlated with significant alteration of the dominant TCR-β chain repertoire expressed by HEL-specific CD4 T cells, suggesting that TSSP is necessary for the intrathymic development of cells expressing these TCRs. Thus, TSSP contributes to the diversification of the functional endogenous CD4 T cell TCR repertoire in the thymus.

scholarly journals Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells

2021 ◽  
Vol 22 (5) ◽  
pp. 2713
Author(s):  
Sun-Hye Shin ◽  
Kyung-Ah Cho ◽  
Hee-Soo Yoon ◽  
So-Yeon Kim ◽  
Hee-Yeon Kim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Acyl Chain ◽  
Signal Strength ◽  
Cell Receptor ◽  
Ceramide Synthase ◽  
Asthmatic Patients

(1) Background: six mammalian ceramide synthases (CerS1–6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22–C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.

scholarly journals Loss of Immunological Tolerance in Gimap5-Deficient Mice Is Associated with Loss of Foxo in CD4+ T Cells

2011 ◽  
Vol 188 (1) ◽  
pp. 146-154 ◽  
Author(s):  
H. Ibrahim Aksoylar ◽  
Kristin Lampe ◽  
Michael J. Barnes ◽  
David R. Plas ◽  
Kasper Hoebe
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Immunological Tolerance ◽  
Deficient Mice

scholarly journals Functional Uncoupling of T-cell Receptor Engagement and Lck Activation in Anergic Human Thymic CD4+T Cells

2001 ◽  
Vol 276 (20) ◽  
pp. 17455-17460 ◽  
Author(s):  
Wakae Fujimaki ◽  
Makio Iwashima ◽  
Junji Yagi ◽  
Hua Zhang ◽  
Hisako Yagi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cell Receptor

scholarly journals CD4+ T Cells from Glutamic Acid Decarboxylase (GAD)65-specific T Cell Receptor Transgenic Mice Are Not Diabetogenic and Can Delay Diabetes Transfer

2002 ◽  
Vol 196 (4) ◽  
pp. 481-492 ◽  
Author(s):  
Kristin V. Tarbell ◽  
Mark Lee ◽  
Erik Ranheim ◽  
Cheng Chi Chao ◽  
Maija Sanna ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Glutamic Acid Decarboxylase ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Acid Decarboxylase ◽  
Gad 65

Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65-specific T cell clone of many identified can transfer diabetes. We have generated transgenic mice on the NOD background expressing a T cell receptor (TCR)-specific for peptide epitope 286–300 (p286) of GAD65. These mice have GAD65-specific CD4+ T cells, as shown by staining with an I-Ag7(p286) tetramer reagent. Lymphocytes from these TCR transgenic mice proliferate and make interferon γ, interleukin (IL)-2, tumor necrosis factor (TNF)-α, and IL-10 when stimulated in vitro with GAD65 peptide 286–300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. CD4+ T cells, or p286-tetramer+CD4+ Tcells, from GAD65 286–300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. This data suggests that GAD65 peptide 286–300-specific T cells have disease protective capacity and are not pathogenic.

scholarly journals S1783 Transferred CD4+ T Cells Induce Tight Junction Assembly Through Notch Signaling Pathway in the Distal Colon of RAG1-/- Deficient Mice

2010 ◽  
Vol 138 (5) ◽  
pp. S-273
Author(s):  
Stephanie Dahan ◽  
Jay C. Unkeless ◽  
Keren M. Rabinowitz ◽  
Paul M. Arnaboldi ◽  
Lloyd Mayer
Keyword(s):  
T Cells ◽  
Tight Junction ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cd4 T Cells ◽  
Distal Colon ◽  
Notch Signaling Pathway ◽  
Deficient Mice

scholarly journals CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway

Blood ◽  
2009 ◽  
Vol 114 (3) ◽  
pp. 580-588 ◽  
Author(s):  
Kathrin Gollmer ◽  
François Asperti-Boursin ◽  
Yoshihiko Tanaka ◽  
Klaus Okkenhaug ◽  
Bart Vanhaesebroeck ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Early Time ◽  
Cell Receptor ◽  
Tcr Signaling ◽  
Activation Markers

Abstract CD4+ T cells use the chemokine receptor CCR7 to home to and migrate within lymphoid tissue, where T-cell activation takes place. Using primary T-cell receptor (TCR)–transgenic (tg) CD4+ T cells, we explored the effect of CCR7 ligands, in particular CCL21, on T-cell activation. We found that the presence of CCL21 during early time points strongly increased in vitro T-cell proliferation after TCR stimulation, correlating with increased expression of early activation markers. CCL21 costimulation resulted in increased Ras- and Rac-GTP formation and enhanced phosphorylation of Akt, MEK, and ERK but not p38 or JNK. Kinase-dead PI3KδD910A/D910A or PI3Kγ-deficient TCR-tg CD4+ T cells showed similar responsiveness to CCL21 costimulation as control CD4+ T cells. Conversely, deficiency in the Rac guanine exchange factor DOCK2 significantly impaired CCL21-mediated costimulation in TCR-tg CD4+ T cells, concomitant with impaired Rac- but not Ras-GTP formation. Using lymph node slices for live monitoring of T-cell behavior and activation, we found that G protein-coupled receptor signaling was required for early CD69 expression but not for Ca2+ signaling. Our data suggest that the presence of CCL21 during early TCR signaling lowers the activation threshold through Ras- and Rac-dependent pathways leading to increased ERK phosphorylation.

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