scholarly journals Faculty Opinions recommendation of Essential roles of CD8+CD122+ regulatory T cells in the maintenance of T cell homeostasis.

2004 ◽  
Author(s):  
Barry Rouse
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
T Cell Homeostasis ◽  
Cell Homeostasis

IL-2 Ameliorates Chronic GVHD by Inducing Antigen-Specific Regulatory T Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2654-2654
Author(s):  
Jens G. Lohr ◽  
Birgit Knoechel ◽  
Estelle C. Kahn ◽  
Abul K. Abbas
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd4 T Cells ◽  
Chronic Gvhd ◽  
The Self ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Peripheral Tissues ◽  
Self Antigen

Abstract We have developed a mouse model in which a GvHD-like syndrome develops in response to a defined soluble self-antigen. This phenotype is caused after transfer of CD4+ T cells that have a single specificity and are reactive to the self-antigen into a lymphopenic host that expresses the cognate antigen. By using a clonotypic antibody we are able to identify these cells and can therefore follow their migration, kinetics and functional characteristics. At least two distinct phases can be identified by clinical picture and correlated with accumulation of T cells - an early phase, resembling acute GvHD, leading to wasting and death coinciding with rapid accumulation of T cells, and a late phase in which a stable number of T cells is maintained clinically reminiscent of chronic GvHD. We show here that a fraction of the naïve T cells that encounter the self-antigen after transfer develop into CD4+CD25+ regulatory T cells (Treg) in the periphery. This population controls T cell homeostasis, activation and severe immune pathology. The development of CD4+CD25+ Treg critically depends on IL-2 produced by the T cells. Therefore, in the absence of IL-2, T cell homeostasis cannot be maintained and massive accumulation of CD4+ T cells leads to severe inflammation of the skin. Importantly, only IL-2 that is produced by the T cells themselves, but not from peripheral tissues, leads to efficient generation of Treg and T cell homeostasis. We suggest that Treg-development is a differentiation step of T cells that encounter self-antigen in the periphery, and is essential for maintaining homeostasis even in the presence of self-recognition. Our data provide mechanistic insight into the re-establishment of homeostasis after cell transfer into a lymphopenic host and have important implications for the use and timing of therapeutic approaches targeting the IL-2 pathway.

scholarly journals Regulatory T cells in the control of T cell homeostasis

2010 ◽  
Vol 30 (6) ◽  
pp. 502-506 ◽  
Author(s):  
Kimito Kawahata ◽  
Takeyuki Kanzaki ◽  
Mitsuru Imamura ◽  
Lisa Akahira ◽  
Kazuya Michishita ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
T Cell Homeostasis ◽  
Cell Homeostasis

scholarly journals SHIP-1 Regulates the Differentiation and Function of Tregs via Inhibiting mTORC1 Activity

2022 ◽  
Author(s):  
Zuochen Du ◽  
Jinzhi Wang ◽  
Di Yang ◽  
Xiaoyu Sun ◽  
Lu Huang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Metabolism ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Signaling Mechanism ◽  
Suppressive Function ◽  
And Function

Abstract Cell metabolism is crucial for orchestrating the differentiation and function of regulatory T cells (Tregs). However, the underlying signaling mechanism that coordinates cell metabolism to regulate Treg activity is not completely understood. As a pivotal molecule in lipid metabolism, the role of SHIP-1 has been studied extensively in B cells and CD4 T cells, yet its regulatory role in Tregs remains unknown. In this study, we generated “SHIP-1 KO mice” that have SHIP-1 specifically deleted in regulatory T cells by crossing Foxp3YFP-cre mice with SHIP-1fl/fl mice. Surprisingly, SHIP-1 KO mice had severe autoimmunity with increased Tregs in the thymus and disrupted peripheral T cell homeostasis. Mechanistically, CD4Cre SHIP-1flox/flox mice were found to have increased Treg precursors and SHIP-1 KO Tregs had reduced migration and stability, which caused decreased Tregs in the spleen. Additionally, the suppressive function of Tregs from SHIP-1 KO mice was diminished, along with their promotion of anti-tumor immunity. Interestingly, the PI3K-mTORC1, but not mTORC2, signaling axis was enhanced in SHIP-1 KO Tregs. In vivo treatment of SHIP-1 KO mice with rapamycin rescued the abnormal Treg percentages and peripheral T cell homeostasis, as well as Treg suppressive function. Furthermore, the treatment of wild-type mice with SHIP-1 inhibitor enhanced anti-tumor activity. Our study has revealed a previously unrecognized underlying function of SHIP-1 in Tregs, which highlights the SHIP-1-PI3K-mTORC1 axis that regulates Treg differentiation and function.

scholarly journals Distinct Effects of STAT5 Activation on CD4+and CD8+T Cell Homeostasis: Development of CD4+CD25+Regulatory T Cells versus CD8+Memory T Cells

2003 ◽  
Vol 171 (11) ◽  
pp. 5853-5864 ◽  
Author(s):  
Matthew A. Burchill ◽  
Christine A. Goetz ◽  
Martin Prlic ◽  
Jennifer J. O’Neil ◽  
Ian R. Harmon ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Memory T Cells ◽  
Cd8 T Cell ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Cd8 Memory T Cells

scholarly journals A unique subpopulation of CD4+ regulatory T cells controls wasting disease, IL-10 secretion and T cell homeostasis

2003 ◽  
Vol 33 (9) ◽  
pp. 2419-2428 ◽  
Author(s):  
Alice Banz ◽  
António Peixoto ◽  
Christiane Pontoux ◽  
Corinne Cordier ◽  
Benedita Rocha ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
T Cell Homeostasis ◽  
Wasting Disease ◽  
Cell Homeostasis

Adoptive transfer of syngeneic T cells in HIV-1 discordant twins indicates rapid regulation of T-cell homeostasis

2007 ◽  
Vol 136 (4) ◽  
pp. 641-648 ◽  
Author(s):  
Christian Hoffmann ◽  
Hans-Juergen Stellbrink ◽  
Thomas Dielschneider ◽  
Olaf Degen ◽  
Albrecht Stoehr ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Discordant Twins ◽  
Hiv 1

scholarly journals PTCy ameliorates GVHD by restoring regulatory and effector T-cell homeostasis in recipients with PD-1 blockade

2019 ◽  
Vol 3 (23) ◽  
pp. 4081-4094 ◽  
Author(s):  
Shuntaro Ikegawa ◽  
Yusuke Meguri ◽  
Takumi Kondo ◽  
Hiroyuki Sugiura ◽  
Yasuhisa Sando ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Effector T Cells ◽  
T Cell Subsets ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Effector T Cell ◽  
Key Points

Key Points PD-1 blockade exacerbated GVHD by altering the homeostasis of Tregs and effector T cells after HSCT. PTCy ameliorated GVHD after PD-1 blockade by restoring the homeostatic balance of T-cell subsets.

scholarly journals TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis

2009 ◽  
Vol 206 (10) ◽  
pp. 2111-2119 ◽  
Author(s):  
Ning Lu ◽  
Yi-Hong Wang ◽  
Yui-Hsi Wang ◽  
Kazuhiko Arima ◽  
Shino Hanabuchi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
T Cell Proliferation ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Th2 Differentiation

Whether thymic stromal lymphopoietin (TSLP) directly induces potent human CD4+ T cell proliferation and Th2 differentiation is unknown. We report that resting and activated CD4+ T cells expressed high levels of IL-7 receptor a chain but very low levels of TSLP receptor (TSLPR) when compared with levels expressed in myeloid dendritic cells (mDCs). This was confirmed by immunohistology and flow cytometry analyses showing that only a subset of mDCs, with more activated phenotypes, expressed TSLPR in human tonsils in vivo. IL-7 induced strong STAT1, -3, and -5 activation and promoted the proliferation of naive CD4+ T cells in the presence of anti-CD3 and anti-CD28 monoclonal antibodies, whereas TSLP induced weak STAT5 activation, associated with marginally improved cell survival and proliferation, but failed to induce cell expansion and Th2 differentiation. The effect of TSLP on enhancing strong human T cell proliferation was observed only when sorted naive CD4+ T cells were cultured with mDCs at levels as low as 0.5%. TSLP could only induce naive CD4+ T cells to differentiate into Th2 cells in the presence of allogeneic mDCs. These results demonstrate that IL-7 and TSLP use different mechanisms to regulate human CD4+ T cell homeostasis.

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