puc-header

High-Resolution Phenotyping of Early Acute Rejection Reveals a Conserved Alloimmune Signature

36 Pages Posted: 24 Apr 2020 Sneak Peek Status: Under Review

See all articles by James T. Harden

James T. Harden

Stanford University - Division of Abdominal Transplantation

Xi Wang

Stanford University - Division of Abdominal Transplantation

Adam Sang

Stanford University - Division of Abdominal Transplantation

Carlos O. Esquivel

Stanford University - Division of Abdominal Transplantation

Olivia M. Martinez

Stanford University - Division of Abdominal Transplantation

Sheri M. Krams

Stanford University - Division of Abdominal Transplantation

More...

Abstract

Alloimmune responses in acute rejection are complex, involving multiple interacting cell types and pathways. Deep profiling of these cell types has been limited by technology that lack the capacity to resolve this high dimensionality. Single-cell mass cytometry was used to characterize the alloimmune response in early acute rejection, measuring 37 parameters simultaneously, across multiple time-points in two models; a well-established murine cardiac and a novel murine vascularized composite allotransplant (VCA). Unsupervised hierarchical clustering was used to group related cell types defined by combinatorial expression of surface and intracellular proteins, along with markers of effector function and activation. This expression profile was mapped to visualize structural changes in antigen composition across cell types, revealing unique phenotypic signatures in alloimmune T cells, NK cells, and myeloid subsets that were conserved and that firmly distinguished rejecting from non-rejecting grafts.

Keywords: Alloimmunity, single cell mass cytometry

Suggested Citation

Harden, James T. and Wang, Xi and Sang, Adam and Esquivel, Carlos O. and Martinez, Olivia M. and Krams, Sheri M., High-Resolution Phenotyping of Early Acute Rejection Reveals a Conserved Alloimmune Signature. Available at SSRN: https://ssrn.com/abstract=3575160 or http://dx.doi.org/10.2139/ssrn.3575160
This is a paper under consideration at Cell Press and has not been peer-reviewed.

James T. Harden

Stanford University - Division of Abdominal Transplantation

United States

Xi Wang

Stanford University - Division of Abdominal Transplantation

United States

Adam Sang

Stanford University - Division of Abdominal Transplantation

United States

Carlos O. Esquivel

Stanford University - Division of Abdominal Transplantation

United States

Olivia M. Martinez

Stanford University - Division of Abdominal Transplantation ( email )

United States

Sheri M. Krams (Contact Author)

Stanford University - Division of Abdominal Transplantation ( email )

United States

Click here to go to Cell.com

Paper statistics

Abstract Views
63
Downloads
5