Pilot Study of Delayed ICOS/ICOS-L Blockade With αCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model

O’Neill, Natalie A.; Braileanu, Gheorghe; Cheng, Xiangfei; Hershfeld, Alena; Sun, Wenji; Reimann, Keith A.; Dahi, Sia; Kubicki, Natalia; Hassanein, Wessam; Laird, Christopher; Cimeno, Arielle; Azimzadeh, Agnes M.; Pierson, Richard N.

doi:10.1097/txd.0000000000000761

Cited by 9 publications

(13 citation statements)

References 52 publications

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“…However, ICOS overexpression on donor-reactive T cells is unable to enhance alloreactive CD8 T cell responses or precipitate acute rejection in a mouse model of skin allotransplant [46]. Also, a delayed ICOS-Ig failed to enhance survival of heart transplants in cynomolgus monkey [47]. Perhaps, in human KTx, ICOS may turn to be more important as suggested by the finding of more abundant ICOS + graft-infiltrating cells accompanied by higher plasma ICOS levels in antibody mediated rejection [48].…”

Section: Discussionmentioning

confidence: 98%

CD16+ Cells and Costimulatory Molecules of Lymphocyte Activation Present inside Human Kidney Grafts and in Blood Circulation

Xavier¹,

Oliveira²

2021

OJNeph

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Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16 + cells on aspiration biopsies of kidney transplants, measured three soluble factors and when indicated tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies were performed either on days seven or 14-30 post-transplantation among stable kidney transplants and on the day of acute rejection diagnosis, while a sample of peripheral blood was collected simultaneously. The cyto preparations were studied by the enzymatic avidin biotin complex staining. The immunocytochemistry was directed to CD16, CD28, CD152, ICOS, CD40, CD154, CD26 and CD27. We performed the analysis in the peripheral blood by ELISA for soluble(s) CD16, CD26, and CD154. Results: The group of acute rejection cases showed a significant up-regulated expression of CD16, CD26, ICOS and CD40 as compared to the group of stable cases. Both sCD16 and sCD154 were significantly higher in the blood samples of the group with acute rejection. Thymoglobulin down-regulated CD154 and sCD16. CD16, CD26 and ICOS exhibited very high sensitivity and specificity for acute rejection diagnosis. Conclusions: The presence of CD16 + cells inside the graft emerged as a distinct player in acute rejection, confirming other previous reports whereas we first document that in human kidney transplants, ICOS and CD26 are significantly up-regulated and both reached positive predictive values for acute rejection ≥ 80%. The other costimulatory molecules, with the exception of CD40, though widely known, did not show robust association with immune events.

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Section: Discussionmentioning

confidence: 98%

CD16+ Cells and Costimulatory Molecules of Lymphocyte Activation Present inside Human Kidney Grafts and in Blood Circulation

Xavier¹,

Oliveira²

2021

OJNeph

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“…More recently, coadministration of ICOS-Ig with anti-CD40 also did not improve survival as compared to anti-CD40 alone in a model of cardiac transplantation in nonhuman primates. 108 The use of anti-ICOS, however, seemed to more effectively block humoral responses in preclinical models. It led to a decreased production of DSAs in a model of islet xenotransplantation.…”

Section: Icos/icos-lmentioning

confidence: 99%

Costimulatory blockade molecules and B-cell–mediated immune response: current knowledge and perspectives

Leibler

Thiolat

Elsner

et al. 2019

Kidney International

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“…In a NHP model of renal transplantation, a one-month lasting regimen of ICOS-Ig along with CD28/CD80 blockage did not significantly influence the renal allograft survival. The augmentation of the expression of ICOS takes place at least 60 days posttransplantation (O'Neill et al, 2018). (Burmeister et al, 2008;Harada et al, 2003;Lo et al, 2015).…”

Section: Inducible Co-stimulator (Icos)mentioning

confidence: 99%

An update on potentials and promises of T cell co‐signaling molecules in transplantation

Mardomi

Mohammadi

Khosroshahi

et al. 2019

Journal Cellular Physiology

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Pilot Study of Delayed ICOS/ICOS-L Blockade With αCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model

Abstract: Supplemental digital content is available in the text.

Cited by 9 publications

References 52 publications

CD16+ Cells and Costimulatory Molecules of Lymphocyte Activation Present inside Human Kidney Grafts and in Blood Circulation

CD16+ Cells and Costimulatory Molecules of Lymphocyte Activation Present inside Human Kidney Grafts and in Blood Circulation

Costimulatory blockade molecules and B-cell–mediated immune response: current knowledge and perspectives

An update on potentials and promises of T cell co‐signaling molecules in transplantation

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