Abstract:
:Human invariant natural killer T (iNKT) cells are a rare innate-like lymphocyte population that recognizes glycolipids presented on CD1d. Studies in mice have shown that these cells are heterogeneous and are capable of enacting diverse functions, and the composition of iNKT cell subsets can alter disease outcomes. In contrast, far less is known about how heterogeneity in human iNKT cells relates to disease. To address this, we used a high-dimensional, data-driven approach to devise a framework for parsing human iNKT heterogeneity. Our data revealed novel and previously described iNKT cell phenotypes with distinct functions. In particular, we found 2 phenotypes of interest: (1) a population with T helper 1 function that was increased with iNKT activation characterized by HLA-II+CD161- expression, and (2) a population with enhanced cytotoxic function characterized by CD4-CD94+ expression. These populations correlate with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation and with new onset type 1 diabetes, respectively. Our study identifies human iNKT cell phenotypes associated with human disease that could aid in the development of biomarkers or therapeutics targeting iNKT cells.
journal_name
Bloodjournal_title
Bloodauthors
Erkers T,Xie BJ,Kenyon LJ,Smith B,Rieck M,Jensen KP,Ji X,Basina M,Strober S,Negrin RS,Maecker HT,Meyer EHdoi
10.1182/blood.2019001903subject
Has Abstractpub_date
2020-03-12 00:00:00pages
814-825issue
11eissn
0006-4971issn
1528-0020pii
431015journal_volume
135pub_type
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