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SIRPα+ DCs and the Time-Dependent CD4+CD8+ Double Positive T Cell Infiltration in Accepted Renal Allografts.

T. Ashry,1,2 C. Yang,2 B. Jiang,2 D. Ndishabandi,2 P. Russel,1,2 R. Colvin,1,2 J. Madsen,1,2 A. Alessandrini.1,2

1HMS, Boston
2MGH, Boston

Meeting: 2017 American Transplant Congress

Abstract number: B41

Keywords: Kidney transplantation, Thymus, Tolerance

Session Information

Session Name: Poster Session B: Allorecognition and T Cell Biology

Session Type: Poster Session

Date: Sunday, April 30, 2017

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Introduction

In 2015 Overgaard and colleagues proposed that double positive T (DPT) cells, usually unique to the thymus, represent more than a developmental phase as extrathymic DPT cells in mice are seen in conditions such as autoimmune disease and tumors. We assessed DPT cells in spontaneous renal allograft acceptance in mice (i.e.DBA/2 to B6) and the relation with SIRPα+CD11c+ dendritic cells (SIRPαDCs) that seem to play a role in Treg induction in the thymus. Our findings relate to prior data suggesting Treg-rich Organized Lymphoid Structures (TOLS) harboring DPT cells in accepted renal allografts display thymic-like properties, such as CD70 staining similar to the thymus.

Methods

We isolated cells from spontaneously accepted fully mismatched renal allografts (DBA/2J in C57/B6 recipient). Kidneys were collagenase type IV-digested (20 minutes) and Ficoll-separated then cells stained with a set antibody panel and analyzed by flow cytometry.

Results

DPT cells, considered rare extrathymically, were found present in DBA to B6 spontaneously accepted renal allografts week 3 post-transplantation Interestingly, reverse B6 to DBA/2 models consistently reject the renal allograft. Considering TOLS also stain CD70 positive, a signaling pathway essential in the thymic medulla, we surmise TOLS may exhibit thymic-like properties. Further evidence of a thymus-like phenotype lies in presence of a subpopulation of dendritic cells expressing SIRPα in naïve DBA but not naïve B6 kidneys (Fisher's P Value <0.0001). Conclusion

We observed time-dependent accumulation of DPT cells in accepted renal allografts at weeks 1,3 & 6 paralleling the formation of TOLS. The structures exhibit thymic-like attributes including SIRPαDCs, present in naïve DBA kidneys and not B6.

CITATION INFORMATION: Ashry T, Yang C, Jiang B, Ndishabandi D, Russel P, Colvin R, Madsen J, Alessandrini A. SIRPα+ DCs and the Time-Dependent CD4+CD8+ Double Positive T Cell Infiltration in Accepted Renal Allografts. Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Ashry T, Yang C, Jiang B, Ndishabandi D, Russel P, Colvin R, Madsen J, Alessandrini A. SIRPα+ DCs and the Time-Dependent CD4+CD8+ Double Positive T Cell Infiltration in Accepted Renal Allografts. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/sirp-dcs-and-the-time-dependent-cd4cd8-double-positive-t-cell-infiltration-in-accepted-renal-allografts/. Accessed May 25, 2025.

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