Biomaterial Database

Inflammasome activation occurs in CD4+ and CD8+ T cells during graft-versus-host disease. 2023

Sarah Talley, and David J Rademacher, and Edward M Campbell

Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.

A severe complication of hematopoietic stem cell transplantation is graft-versus-host disease (GvHD), a reaction that occurs following the transfer of donor immune cells (the graft) into an allogeneic host. Transplanted cells recognize host alloantigens as foreign, resulting in the activation of donor T cells and migration of these pathological cells into host tissues. In this study, we found that caspase-1 is activated in alloreactive murine and human CD4+ and CD8+ T cells early during acute GvHD (aGvHD). The presence of inflammasome-bound active caspase-1 (p33) and ASC-speck formation confirmed inflammasome activation in these cells. We further measured gasdermin D (GSDMD) cleavage and IL-18 secretion from alloreactive T cells ex vivo. Isolated T cells with high levels of active caspase-1 had a strong inflammatory transcriptional signature and a metabolic phenotype similar to inflammatory myeloid cells, including the upregulation of proinflammatory cytokines and metabolic switch from oxidative phosphorylation to aerobic glycolysis. We also observed oxidative stress, mitochondrial dysfunction, and cell death phenotypes consistent with inflammatory cell death in alloreactive T cells. For the first time, this study characterizes caspase-1 activation in transplanted T cells during aGvHD, using mouse and human models, adding to a body of literature supporting inflammasome function in cells of the adaptive immune system.

UI	MeSH Term	Description	Entries
D006086	Graft vs Host Disease	The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.	Graft-Versus-Host Disease,Homologous Wasting Disease,Runt Disease,Graft-vs-Host Disease,Disease, Graft-Versus-Host,Disease, Graft-vs-Host,Disease, Homologous Wasting,Disease, Runt,Diseases, Graft-Versus-Host,Diseases, Graft-vs-Host,Graft Versus Host Disease,Graft-Versus-Host Diseases,Graft-vs-Host Diseases
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015496	CD4-Positive T-Lymphocytes	A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.	T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D058847	Inflammasomes	Multiprotein complexes that mediate the activation of CASPASE-1. Dysregulation of inflammasomes has also been linked to a number of autoinflammatory and autoimmune disorders.	Inflammasome,Pyroptosome,Pyroptosomes
D018414	CD8-Positive T-Lymphocytes	A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.	Suppressor T-Lymphocytes, CD8-Positive,T8 Cells,T8 Lymphocytes,CD8-Positive Lymphocytes,Suppressor T-Cells, CD8-Positive,CD8 Positive Lymphocytes,CD8 Positive T Lymphocytes,CD8-Positive Lymphocyte,CD8-Positive Suppressor T-Cell,CD8-Positive Suppressor T-Cells,CD8-Positive Suppressor T-Lymphocyte,CD8-Positive Suppressor T-Lymphocytes,CD8-Positive T-Lymphocyte,Cell, T8,Cells, T8,Lymphocyte, CD8-Positive,Lymphocyte, T8,Lymphocytes, CD8-Positive,Lymphocytes, T8,Suppressor T Cells, CD8 Positive,Suppressor T Lymphocytes, CD8 Positive,Suppressor T-Cell, CD8-Positive,Suppressor T-Lymphocyte, CD8-Positive,T-Cell, CD8-Positive Suppressor,T-Cells, CD8-Positive Suppressor,T-Lymphocyte, CD8-Positive,T-Lymphocyte, CD8-Positive Suppressor,T-Lymphocytes, CD8-Positive,T-Lymphocytes, CD8-Positive Suppressor,T8 Cell,T8 Lymphocyte
D020170	Caspase 1	A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.	ICE Protease,IL-1 beta-Converting Enzyme,Interleukin-1beta Converting Enzyme,CASP1 Caspase,IL-1 beta Convertase,IL1BC Enzyme,Interleukin-1 Converting Enzyme,Pro-Caspase-1,Procaspase-1,Caspase, CASP1,Convertase, IL-1 beta,Converting Enzyme, Interleukin-1,Converting Enzyme, Interleukin-1beta,IL 1 beta Convertase,IL 1 beta Converting Enzyme,Interleukin 1 Converting Enzyme,Interleukin 1beta Converting Enzyme,Pro Caspase 1,Procaspase 1,beta Convertase, IL-1,beta-Converting Enzyme, IL-1