Early T Cell Activation Metrics Predict Graft-versus-Host Disease in a Humanized Mouse Model of Hematopoietic Stem Cell Transplantation. J Immunol 2020 Jul 01;205(1):272-281
Date
05/24/2020Pubmed ID
32444392Pubmed Central ID
PMC7329317DOI
10.4049/jimmunol.2000054Scopus ID
2-s2.0-85088373153 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
Acute graft-versus-host disease (GVHD) is a frequent complication of hematopoietic transplantation, yet patient risk stratification remains difficult, and prognostic biomarkers to guide early clinical interventions are lacking. We developed an approach to evaluate the potential of human T cells from hematopoietic grafts to produce GVHD. Nonconditioned NBSGW mice transplanted with titrated doses of human bone marrow developed GVHD that was characterized by widespread lymphocyte infiltration and organ pathology. Interestingly, GVHD was not an inevitable outcome in our system and was influenced by transplant dose, inflammatory status of the host, and type of graft. Mice that went on to develop GVHD showed signs of rapid proliferation in the human T cell population during the first 1-3 wk posttransplant and had elevated human IFN-γ in plasma that correlated negatively with the expansion of the human hematopoietic compartment. Furthermore, these early T cell activation metrics were predictive of GVHD onset 3-6 wk before phenotypic pathology. These results reveal an early window of susceptibility for pathological T cell activation following hematopoietic transplantation that is not simply determined by transient inflammation resulting from conditioning-associated damage and show that T cell parameters during this window can serve as prognostic biomarkers for risk of later GVHD development.
Author List
Hess NJ, Hudson AW, Hematti P, Gumperz JEAuthors
Peiman Hematti MD Professor in the Medicine department at Medical College of WisconsinAmy W. Hudson PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCell Proliferation
Cells, Cultured
Disease Models, Animal
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Interferon-gamma
Lymphocyte Activation
Male
Mice
Postoperative Period
Primary Cell Culture
Prognosis
T-Lymphocytes
Time Factors
Transplantation Chimera
Transplantation Conditioning
Transplantation, Heterologous
