scholarly journals Conversion of antigen-specific effector/memory T cells into Foxp3-expressing Treg cells by inhibition of CDK8/19

2019 ◽  
Vol 4 (40) ◽  
pp. eaaw2707 ◽  
Author(s):  
Masahiko Akamatsu ◽  
Norihisa Mikami ◽  
Naganari Ohkura ◽  
Ryoji Kawakami ◽  
Yohko Kitagawa ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Cell Function ◽  
Memory T Cells ◽  
Contact Hypersensitivity ◽  
Effector Memory ◽  
Skin Contact ◽  
Effector Memory T Cells ◽  
Specific Effector

A promising way to restrain hazardous immune responses, such as autoimmune disease and allergy, is to convert disease-mediating T cells into immunosuppressive regulatory T (Treg) cells. Here, we show that chemical inhibition of the cyclin-dependent kinase 8 (CDK8) and CDK19, or knockdown/knockout of the CDK8 or CDK19 gene, is able to induce Foxp3, a key transcription factor controlling Treg cell function, in antigen-stimulated effector/memory as well as naïve CD4+ and CD8+ T cells. The induction was associated with STAT5 activation, independent of TGF-β action, and not affected by inflammatory cytokines. Furthermore, in vivo administration of a newly developed CDK8/19 inhibitor along with antigen immunization generated functionally stable antigen-specific Foxp3+ Treg cells, which effectively suppressed skin contact hypersensitivity and autoimmune disease in animal models. The results indicate that CDK8/19 is physiologically repressing Foxp3 expression in activated conventional T cells and that its pharmacological inhibition enables conversion of antigen-specific effector/memory T cells into Foxp3+ Treg cells for the treatment of various immunological diseases.

scholarly journals Unidirectional development of CD8+ central memory T cells into protectiveListeria-specific effector memory T cells

2006 ◽  
Vol 36 (6) ◽  
pp. 1453-1464 ◽  
Author(s):  
Katharina M. Huster ◽  
Martina Koffler ◽  
Christian Stemberger ◽  
Matthias Schiemann ◽  
Hermann Wagner ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Central Memory ◽  
Effector Memory ◽  
Central Memory T Cells ◽  
Effector Memory T Cells ◽  
Specific Effector

scholarly journals Circulating HLA-DR+CD4+ effector memory T cells resistant to CCR5 and PD-L1 mediated suppression compromise regulatory T cell function in tuberculosis

2018 ◽  
Vol 14 (9) ◽  
pp. e1007289 ◽  
Author(s):  
Asma Ahmed ◽  
Vasista Adiga ◽  
Soumya Nayak ◽  
J. Anto Jesuraj Uday Kumar ◽  
Chirag Dhar ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cell ◽  
Cell Function ◽  
Memory T Cells ◽  
Effector Memory ◽  
Effector Memory T Cells ◽  
T Cell Function ◽  
Hla Dr

A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo

Blood ◽  
2008 ◽  
Vol 111 (10) ◽  
pp. 5008-5016 ◽  
Author(s):  
Sophie Guia ◽  
Céline Cognet ◽  
Ludovic de Beaucoudrey ◽  
Marlowe S. Tessmer ◽  
Emmanuelle Jouanguy ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Memory T Cells ◽  
Effector Memory ◽  
Similar Data ◽  
Effector Memory T Cells ◽  
Ifn Γ

Abstract Natural killer (NK) cells have been originally defined by their “naturally occurring” effector function. However, only a fraction of human NK cells is reactive toward a panel of prototypical tumor cell targets in vitro, both for the production of interferon-γ (IFN-γ) and for their cytotoxic response. In patients with IL12RB1 mutations that lead to a complete IL-12Rβ1 deficiency, the size of this naturally reactive NK cell subset is diminished, in particular for the IFN-γ production. Similar data were obtained from a patient with a complete deficit in IL-12p40. In addition, the size of the subset of effector memory T cells expressing CD56 was severely decreased in IL-12Rβ1– and IL-12p40–deficient patients. Human NK cells thus require in vivo priming with IL-12/23 to acquire their full spectrum of functional reactivity, while T cells are dependent upon IL-12/23 signals for the differentiation and/or the maintenance of CD56+ effector memory T cells. The susceptibility of IL-12/23 axis–deficient patients to Mycobacterium and Salmonella infections in combination with the absence of mycobacteriosis or salmonellosis in the rare cases of human NK cell deficiencies point to a role for CD56+ T cells in the control of these infections in humans.

scholarly journals Lineage relationships, homeostasis, and recall capacities of central– and effector–memory CD8 T cells in vivo

2005 ◽  
Vol 201 (4) ◽  
pp. 579-590 ◽  
Author(s):  
Cécile Bouneaud ◽  
Zacarias Garcia ◽  
Philippe Kourilsky ◽  
Christophe Pannetier
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Receptor Repertoire ◽  
Effector Memory T Cells ◽  
Secondary Challenge ◽  
Short Time

The lineage relationships of central–memory T cells (TCM) cells and effector–memory T cells (TEM), as well as their homeostasis and recall capacities, are still controversial. We investigated these issues in a murine model using two complementary approaches: T cell receptor repertoire analysis and adoptive transfer experiments of purified H-Y–specific TCM and TEM populations. Repertoire studies showed that approximately two thirds of TCM and TEM clones derived from a common naive precursor, whereas the other third was distinct. Both approaches highlighted that TCM and TEM had drastically distinct behaviors in vivo, both in the absence of antigen or upon restimulation. TCM clones were stable in the absence of restimulation and mounted a potent and sustained recall response upon secondary challenge, giving rise to both TCM and TEM, although only a fraction of TCM generated TEM. In contrast, TEM persisted for only a short time in the absence of antigen and, although a fraction of them were able to express CD62L, they were unable to mount a proliferative response upon secondary challenge in this model.

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