Articles tagged "Co-stimulation"

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…
2017 American Transplant Congress
Dual Targeting of Costimulation and Proteasome to Desensitize and Prolong Graft Survival of Sensitized Nonhuman Primates.
J. Kwun,¹ C. Burghuber,¹ M. Manook,¹ B. Ezekian,¹ J. Park,^1,2 K. Freishlag,¹ J. Yoon,¹ N. Iwakoshi,³ A. Farris,⁴ S. Knechtle.¹
¹Surgery, Duke Transplant Center, Durham, NC; ²Surgery, Samsung Medical Center, Seoul, Korea; ³Surgery, Emory Transplant Center, Atlanta, GA; ⁴Pathology, Emory University, Atlanta, GA
[Background] Pre-formed donor-specific anti-HLA antibodies (DSA) from prior transplantation, transfusion, or pregnancy affects a significant portion (35%) of patients awaiting a kidney transplant. Highly sensitized…
2017 American Transplant Congress
FcγRIIB-Mediated Coinhibition Attenuates Donor-Reactive CD8+ T Cell Responses.
A. Morris, D. Pinelli, D. Liu, M. Ford.
Emory Transplant Center, Emory University, Atlanta, GA
Memory T cells can be a formidable barrier to long-term, rejection-free allograft survival, particularly in the setting of costimulation blockade. Ongoing work in the field…
2017 American Transplant Congress
Immunoregulatory Roles of CD137 Signaling in Graft-versus-Host Disease.
H. Cho,^1,2 J. Kim,¹ B. Kwon,^1,3 J. Lee,^1,4 K. Park.^1,4
¹Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan, Republic of Korea; ²Departments of Surgery, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan, Republic of Korea; ³School of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea; ⁴Department of Internal Medicine, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan, Republic of Korea
CD137 functions mainly as a costimulatory molecule for T cell activation. However, its functions have been found in a variety of other immune and nonimmune…
2017 American Transplant Congress
mTOR Inhibition Diminishes Peripheral Blood CD8⁺CD28^–CD38^hi Effector/Memory T Cells and Facilitates Resolution of Belatacept-Refractory Kidney Rejection.
C. Castro-Rojas,¹ A. Godarova,¹ A. Leino,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
Belatacept, a CD28-CD80/86 blocker, was approved by the FDA to provide immunosuppression without nephrotoxicity or cardiovascular and metabolic adverse effects. As part of our multi-center…
2017 American Transplant Congress
CD4 Depletion Is Necessary and Sufficient for Long-Term Nonhuman Primate Xenotransplant Survival.
S. Kim, L. Higginbotham, D. Mathews, C. Breeden, A. Stephenson, C. Larsen, M. Ford, J. Tector, A. Adams.
Emory Transplant Center, Emory University, Atlanta, GA; University of Alabama Birmingham, Birmingham, AL
Introduction. Xenotransplantation may alleviate the organ shortage, yet experimental renal xenotransplant has met limited success. We have previously reported the longest surviving pig-to-nonhuman primate (NHP)…
2017 American Transplant Congress
Focal Segmental Glomerulosclerosis Recurrence in Renal Transplant Recipients Treated with Belatacept.
W. Kitchens, A. Farris, S. Pastan, T. Pearson, C. Larsen, A. Adams.
Emory Transplant Center, Atlanta, GA
Introduction: Focal segmental glomerulosclerosis (FSGS) is a cause of end-stage renal failure that frequently recurs following renal transplant, often leading to allograft loss. A recently…