Human monocytes as intermediaries between allogeneic endothelial cells and allospecific T cells: A role for direct scavenger receptor-mediated endothelial membrane uptake in the initiation of alloimmunity

He Xu*, Kiran K. Dhanireddy, Allan D. Kirk

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Recipient monocytes, T cells, and donor endothelial cells (ECs) are recognized as critical components of allograft rejection. We have recently shown that human monocytes infiltrate vascularized allografts before clinical rejection and have thus hypothesized that monocytes, rather than costimulation-poor ECs, initiate an alloimmune response. However, the nature of the interactions between ECs, monocytes, and T cells has been incompletely defined. Specifically, it is not clear whether these cells interact in a hierarchical manner, nor is it apparent what constitutes an interaction. We therefore studied human ECs, monocytes, and T cells in various isolated in vitro combinations to define the salient features of their contact and to determine whether their interactions were sequential in nature. We find that T cells proliferate poorly to allogeneic ECs and autologous monocytes but well to autologous monocytes following allogeneic EC contact. We show that monocytes gain their stimulatory capacity by phagocytizing allogeneic but not autologous EC membranes in a process governed by scavenger receptors. This process facilitates the subsequent presentation of intact donor HLA molecules to T cells (semidirect presentation). Moreover, monocytes are receptive to T cell help only after exposure to ECs and require CD4+ T cells to optimally express costimulatory molecules and foster Ag presentation. Our results indicate that monocytes engage allogeneic ECs through scavenger receptors and are then primed to facilitate T cell activation in a codependent manner. This reciprocal codependence allows for monocytes to serve as a regulated bridge between the allograft and T cells.

Original languageEnglish
Pages (from-to)750-761
Number of pages12
JournalJournal of Immunology
Volume176
Issue number2
DOIs
StatePublished - 15 Jan 2006
Externally publishedYes

Fingerprint

Dive into the research topics of 'Human monocytes as intermediaries between allogeneic endothelial cells and allospecific T cells: A role for direct scavenger receptor-mediated endothelial membrane uptake in the initiation of alloimmunity'. Together they form a unique fingerprint.

Cite this