Unique features and clinical importance of acute alloreactive immune responses

JCI Insight
Charlotte InmanPaul Moss

Abstract

Allogeneic stem cell transplantation (allo-SCT) can cure some patients with hematopoietic malignancy, but this relies on the development of a donor T cell alloreactive immune response. T cell activity in the first 2 weeks after allo-SCT is crucial in determining outcome, despite the clinical effects of the early alloreactive immune response often not appearing until later. However, the effect of the allogeneic environment on T cells is difficult to study at this time point due to the effects of profound lymphopenia. We approached this problem by comparing T cells at week 2 after allograft to T cells from autograft patients. Allograft T cells were present in small numbers but displayed intense proliferation with spontaneous cytokine production. Oligoclonal expansions at week 2 came to represent a substantial fraction of the established T cell pool and were recruited into tissues affected by graft-versus-host disease. Transcriptional analysis uncovered a range of potential targets for immune manipulation, including OX40L, TWEAK, and CD70. These findings reveal that recognition of alloantigen drives naive T cells toward a unique phenotype. Moreover, they demonstrate that early clonal T cell responses are recruited to sites of subs...Continue Reading

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Citations

Mar 23, 2019·International Journal of Molecular Sciences·Caroline MangareBritta Eiz-Vesper
Feb 1, 2020·Oncoimmunology·Isaure VanmeerbeekAbhishek D Garg

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Datasets Mentioned

BETA
GSE36476
GSE111377

Methods Mentioned

BETA
FACS
biopsy
FCS
density gradient centrifugation
PCR
electrophoresis
flow cytometry
RNA-Seq

Software Mentioned

Excel
GAGE
Fastq
GSEA
biomaRt
R
Kaluza
ImmunoSEQ
Ensembl
GraphPad Prism

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