scholarly journals A short course of Tofacitinib sustains the immunoregulatory effect of CTLA4‐Ig in presence of inflammatory cytokines and promotes long‐term survival of murine cardiac allografts

2020 ◽  
Author(s):  
Marcos Iglesias ◽  
Saami Khalifian ◽  
Byoung Chol Oh ◽  
Yichuan Zhang ◽  
Devin Miller ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Term Survival ◽  
Long Term Survival ◽  
Short Course ◽  
Cardiac Allografts

SHORT COURSE TREATMENT OF CYCLOPHOSPHAMIDE INDUCES LONG TERM SURVIVAL OF INTESTINAL ALLOGRAFTS IN MICE

1998 ◽  
Vol 66 (8) ◽  
pp. S25
Author(s):  
R Kellersmann ◽  
R Zhong ◽  
B Garcia ◽  
A Bl??mer ◽  
Z Zhang ◽  
...  
Keyword(s):  
Term Survival ◽  
Long Term Survival ◽  
Short Course

ICOS-Ig combined with CsA induces long term survival of cardiac allografts in mouse

2009 ◽  
Vol 24 (5) ◽  
pp. 249-258
Author(s):  
Zhang Peng ◽  
Wang Zhenmeng ◽  
Qin Qin ◽  
Tang Yi ◽  
Wang Quanxing ◽  
...  
Keyword(s):  
Term Survival ◽  
Long Term Survival ◽  
Cardiac Allografts

Combination Treatment with Donor-Specific Transfusions and Cyclosporine A Induces Long-Term Survival of Cardiac Allografts in Miniature Swine

2005 ◽  
Vol 80 (9) ◽  
pp. 1275-1282 ◽  
Author(s):  
Ruediger Hoerbelt ◽  
Douglas R. Johnston ◽  
Tsuyoshi Shoji ◽  
Stuart L. Houser ◽  
Rebecca S. Hasse ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Combination Treatment ◽  
Miniature Swine ◽  
Term Survival ◽  
Long Term Survival ◽  
Cardiac Allografts

scholarly journals A short course of Tofacitinib sustains the immunoregulatory effect of CTLA4-Ig in presence of inflammatory cytokines and promotes long-term survival of murine cardiac allografts

2020 ◽  
Author(s):  
Marcos Iglesias ◽  
Saami Khalifian ◽  
Byoung Chol Oh ◽  
Yichuan Zhang ◽  
Devin Miller ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Cytokines ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytokine Signaling ◽  
Term Survival ◽  
Long Term Survival ◽  
Promising Strategy

AbstractCostimulation blockade-based regimens are a promising strategy for management of transplant recipients. However, maintenance immunosuppression via CTLA4-Ig monotherapy is characterized by high frequency of rejection episodes. Recent evidence suggests that inflammatory cytokines contribute to alloreactive T cell activation in a CD28-independent manner, a reasonable contributor to the limited efficacy of CTLA4-Ig. In this study, we investigated the possible synergism of a combined short-term inhibition of cytokine signaling and CD28 engagement on the modulation of rejection. Our results demonstrate that the JAK/STAT inhibitor Tofacitinib restored the immunomodulatory effect of CTLA4-Ig on mouse alloreactive T cells in presence of inflammatory cytokines. Tofacitinib exposure conferred dendritic cells with a tolerogenic phenotype reducing their cytokine secretion and costimulatory molecules expression. JAK inhibition also directly affected T cell activation. In vivo, the combination of CTLA4-Ig and Tofacitinib induced long-term survival of heart allografts and, importantly, it was equally effective when using grafts subjected to prolonged ischemia. Transplant survival correlated with a reduction in effector T cells and intragraft accumulation of regulatory T cells. Collectively, our studies demonstrate a powerful synergism between CTLA4-Ig and Tofacitinib and suggest their combined use is a promising strategy for improved management of transplanted patients.

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