scholarly journals CD4+ invariant natural killer T cells protect from murine GVHD lethality through expansion of donor CD4+CD25+FoxP3+ regulatory T cells

Blood ◽  
2014 ◽  
Vol 124 (22) ◽  
pp. 3320-3328 ◽  
Author(s):  
Dominik Schneidawind ◽  
Antonio Pierini ◽  
Maite Alvarez ◽  
Yuqiong Pan ◽  
Jeanette Baker ◽  
...  

Key Points Low doses of adoptively transferred donor CD4+ iNKT cells protect from GVHD while preserving graft-versus-tumor effects. Donor CD4+ iNKT cells inhibit proliferation of alloreactive T cells and promote robust expansion of donor Tregs.

Blood ◽  
2017 ◽  
Vol 129 (23) ◽  
pp. 3121-3125 ◽  
Author(s):  
Jing Du ◽  
Katelyn Paz ◽  
Govindarajan Thangavelu ◽  
Dominik Schneidawind ◽  
Jeanette Baker ◽  
...  

Key Points Low doses of donor iNKT infusion prevent and reverse murine cGVHD. iNKT efficacy in treating established cGVHD is dependent on donor Treg expansion.


Blood ◽  
2015 ◽  
Vol 125 (22) ◽  
pp. 3491-3500 ◽  
Author(s):  
Dominik Schneidawind ◽  
Jeanette Baker ◽  
Antonio Pierini ◽  
Corina Buechele ◽  
Richard H. Luong ◽  
...  

Key Points Low doses of adoptively transferred third-party CD4+ iNKT cells protect from lethal GVHD while preserving graft-versus-tumor effects. Third-party CD4+ iNKT cells are rejected early after transplantation yet protect from GVHD lethality through donor Tregs.


2014 ◽  
Vol 75 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Daithi S. Heffernan ◽  
Sean F. Monaghan ◽  
Chun-Shiang Chung ◽  
William G. Cioffi ◽  
Stefan Gravenstein ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261727
Author(s):  
Chien-Ya Hsu ◽  
Yu-Shan Chueh ◽  
Ming-Ling Kuo ◽  
Pei-Tzu Lee ◽  
Hsiu-Shan Hsiao ◽  
...  

CD1d-restricted invariant natural killer T cells (iNKT cells) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-15 is a pro-inflammatory cytokine which is over-expressed in SLE patients. In the present study, we investigated the iNKT cell expansion of mononuclear cells (MNCs) from SLE patients following 10 days’ culture with α-galactosylceramide (α-Galcer) and /or IL-15. We sought to determine the phenotypic and functional characteristics of the expanded iNKT cells compared to healthy controls and correlated with disease activity. We observed that 1. The percentages of Vα24+/Vβ11+ iNKT cells following 10-day incubation was lower in SLE groups compared to controls; 2. The percentages and absolute numbers of Vα24+/Vβ11+ iNKT cells were expanded by α-galactosylceramide (α-Galcer), and further enhanced with IL-15 in SLE patient, but the effect of IL-15 was much lower than controls; 3.IL-15 +α-Galcer expanded CD3+/CD56+ NKT-like cells from SLE patients, especially with active disease 4. The CD161+ Vα24+/Vβ11+ iNKT cells in SLE were more responsive to α-Galcer stimulation than the CD161- counterpart; 5. IL-15 decreased apoptosis of α-Galcer activated SLE iNKT cells; 6. IL-15 enhanced CD69, CD1d and CD11a expression on α-Galcer treated iNKT cells; 7. The IL-4 production of iNKT cells was decreased in SLE patients compared to controls; 8. IL-15 increased IFN-γ and IL-4 production of SLE iNKT cells; 8. IL-15 failed to augment the ability of iNKT cells to aid NK-mediated K562 cytolysis in SLE patients; 9. CD161 positivity, granzyme B and perforin expression of α-Galcer+IL-15 expanded iNKT cells correlated with C3 levels in SLE patients. Taken together, our results demonstrated numeric and functional deficiency of iNKT cells and their response to IL-15 in SLE patients. Our finding may provide insight for using adoptive iNKT cell therapy in autoimmune diseases.


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