Articles tagged "Co-stimulation"

2018 American Transplant Congress
Ex Vivo Expanded Regulatory T Cells Combined with Short-Term Costimulation Blockade Prevent Rejection of Vascularized Composite Allografts
B. Oh,¹ G. Furtmüller,¹ M. Grzelak,¹ L. Vuong,² M. Iglesias,¹ M. Fryer,¹ D. Cooney,¹ W. Lee,¹ G. Raimondi,¹ G. Brandacher.¹
¹Plastic and Reconstructive Surgery, Johns Hopkins SOM, Baltimore; ²Washington University in St. Louis SOM, St. Louis.
[Background] Reconstructive transplantation represents a valid therapeutic option after devastating tissue loss. Routine clinical application, however, is hampered by the toxicity of long-term maintenance immunosuppression.…
2018 American Transplant Congress
Belatacept-Refractory CD8⁺CD28^–CD38^hi Effector/Memory T Cells Are Targeted by mTOR Inhibition Leading to a Preferential Loss of CD40L
C. Castro Rojas,¹ A. Godarova,¹ A. Rike Shields,² R. Alloway,² M. Jordan,³ E. Woodle,² D. Hildeman.¹
¹Division of Immunobiology, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, OH; ²Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati, OH; ³Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Research Foundation, Cincinnati, OH.
Calcineurin inhibitors (CNIs) and corticosteroids (CSS) have substantial untoward side effects, most notably nephrotoxicity. Consequently, the FDA approved belatacept for maintenance immunosuppression. We recently completed…
2018 American Transplant Congress
B Cell Reconstitution: 36-Month Analysis of Patients Post-Alemtuzumab Induction Followed by Belatacept-Based Immunosuppression
Q. Gao,¹ A. Mehta,² A. Guasch,² A. Ghali,² A. Kirk,¹ H. Xu.¹
¹Department of Surgery, Duke University Medical Center, Durham, NC; ²Emory Transplant Center, Emory University School of Medicine, Atlanta, GA.
Alemtuzumab induction combined with belatacept and rapamycin (ABR) maintenance immunotherapy effectively prevents costimulation blockade resistant rejection (CoBRR). We longitudinally investigated kinetics of repopulating B cell…
2018 American Transplant Congress
De Novo Belatacept in Clinical Vascularized Composite Allotransplantation
L. C. Cendales,¹ D. S. Ruch,² A. R. Cardones,³ G. Potter,⁴ J. Dooley,⁵ D. Dore,⁶ J. Orr,¹ G. Ruskin,⁶ M. Song,¹ D. Chen,⁷ A. Selim,⁷ A. D. Kirk.¹
¹Surgery, Duke University, Durham, NC; ²Orthopedics, Duke University, Durham, NC; ³Dermatology, Duke University, Durham, NC; ⁴Psychiatry and Behavioral Sciences, Duke University, Durham, NC; ⁵Anesthesiology, Duke University, Durham, NC; ⁶Psysical and Occupational Therapy, Duke University, Durham, NC; ⁷Pathology, Duke University, Durham, NC.
Most immunosuppressive regimens in vascularized composite allotransplantation (VCA) have been calcineurin inhibitor (CNI)–based. Costimulation blockade has emerged as a replacement for CNI–based regimens in kidney…
2018 American Transplant Congress
Emergence of a Costimulation-Susceptible T Cell Repertoire Post-Alemtuzumab Induction
Q. Gao,¹ A. Mehta,² A. Guasch,² L. Stempora,¹ A. Kirk,¹ H. Xu.¹
¹Department of Surgery, Duke University Medical Center, Durham, NC; ²Emory Transplant Center, Emory University School of Medicine, Atlanta, GA.
Kidney transplant patients treated with belatacept-based regimens without depletional induction have higher rates of costimulation blockade resistant rejection (CoBRR). In contrast, belatacept effectively prevents rejection…
2018 American Transplant Congress
OX40 Costimulation Prevents Induction of Foxp3⁺ Tregs through Upregulation of Novel Repressors of Foxp3 Gene Expression
X. Zhang,¹ X. Xiao,¹ P. Lan,¹ J. Li,¹ Y. Dou,¹ W. Chen,¹ N. Ishii,² S. Chen,¹ E. Taparowsky,³ X. Li.^1,4
¹Immunobiology & Transplant Research Center, Houston Methodist Hospital, Houston, TX; ²Department of Microbiology and Immunology, Tohoku University, Sendai, Japan; ³Department of Biological Sciences, Perdue University, Lafayette, IN; ⁴Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY.
Foxp3+ Tregs are essential for the induction of transplant tolerance and OX40 costimulation is known to break transplant tolerance. The exact mechanism of OX40 in…
2018 American Transplant Congress
Patients Converted to Belatacept Show Different Immunophenotyping Compared with De Novo Belatacept-Treated Patients
M. Rial,¹ F. Caro,² A. Nella,² D. Guerrieri,² L. León,¹ P. Uva,¹ E. Chuluyan,² D. Casadei.¹
¹Instituto de Nefrología, Nephrology, Buenos Aires, Argentina; ²CEFYBO, UBA, CONICET, Buenos Aires, Argentina.
The incidence of adverse clinical events mainly in early, but not late post-transplantation such as an increased rate of acute rejection precludes the use of…
2018 American Transplant Congress
Loss of HIF-1α in CD4 T Cell Improve Outcome of Mouse Vascularized Osteomyocutaneous Allotransplantation under Costimulation Blockade
C-.H. Lin,^1,2 M. Anggelia,^1,2 H. Yang,³ W. Chuang,⁴ H. Cheng,¹ F-.C. Wei,^1,2 G. Brandacher.⁵
¹PRS, Center for VCA, Chang Gung Memorial Hospital, Taoyuan, Taiwan; ²Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan; ³Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; ⁴Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; ⁵PRS, Johns Hopkins University School of Medicine, Baltimore, MD.
Background: Allograft survival depends on the balance of effector T cells (Teff) and regulatory T cells (Tregs). Previous study suggested that the balance is controlled…
2018 American Transplant Congress
Thymic Irradiation as a Maneuver for Repertoire Exchange in Costimulatory-Blockade-Based Immunotherapy
M. Mulvihill,¹ B. Ezekian,¹ Q. Gao,¹ K. Samy,¹ R. Davis,¹ F. Leopardi,¹ W. Giles,² F-.F. Yin,² C. Willett,² B. Collins,¹ A. Kirk.¹
¹Department of Surgery, Duke University, Durham, NC; ²Department of Radiation Oncology, Duke University, Durham, NC.
Background All successful, prospective clinical tolerance-induction strategies have employed thymic irradiation to achieve chimerism. However, evidence suggests durable chimerism is not required to attain tolerance.…
2018 American Transplant Congress
Graft Dendritic Cell p40 Homodimers Activate Donor-Reactive Endogenous Memory CD8 T Cells within Higher Risk Allografts
H. Tsuda, A. Valujskikh, R. Fairchild.
Immunology, Cleveland Clinic, Cleveland, OH.
Memory T cells with donor-reactivity pose a major barrier to successful allograft transplantation and tolerance induction. Longer cold ischemic storage (CIS) prior to transplantation promotes…