Multivariate Analysis Using High Definition Flow Cytometry Reveals Distinct T Cell Repertoires between the Fetal–Maternal Interface and the Peripheral Blood

Michelle A Neller,Steven Joung,Peter Hsu,Scott R Burrows,Ralph Nanan,Brigitte Santner-Nanan,John J Miles,Rebekah M Brennan

doi:10.3389/fimmu.2014.00033

Abstract

The human T cell compartment is a complex system and while some information is known on repertoire composition and dynamics in the peripheral blood, little is known about repertoire composition at different anatomical sites. Here, we determine the T cell receptor beta variable (TRBV) repertoire at the decidua and compare it with the peripheral blood during normal pregnancy and pre-eclampsia. We found total T cell subset disparity of up to 58% between sites, including large signature TRBV expansions unique to the fetal–maternal interface. Defining the functional nature and specificity of compartment-specific T cells will be necessary if we are to understand localized immunity, tolerance, and pathogenesis.

Highlights

INTRODUCTION αβT cells recognize antigens via the heterodimeric T cell receptor (TR), which is comprised of one alpha (TRA) chain and one beta (TRB) chain
We found total T cell subset disparity of up to 58% between sites, including large signature T cell receptor beta variable (TRBV) expansions unique to the fetal–maternal interface
Large differences in T cell repertoire profile have been observed between peripheral blood mononuclear cells (PBMC) and colon tissue [2], with colon-resident T cells expressing a much more restricted TRBV signature [3]

Summary

Introduction

INTRODUCTION αβT cells recognize antigens via the heterodimeric T cell receptor (TR), which is comprised of one alpha (TRA) chain and one beta (TRB) chain. We determine the T cell receptor beta variable (TRBV) repertoire at the decidua and compare it with the peripheral blood during normal pregnancy and pre-eclampsia. Using multiparametric flow cytometry-based phenotyping and TRBV dissection, we assessed the DMC repertoires of CD8+ CD4+ and Treg cells from women with healthy pregnancies and pre-eclampsia and compared these repertoires with corresponding subsets in peripheral blood.

Results

Conclusion