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| Status |
Public on Nov 17, 2016 |
| Title |
Expression Profile of alloreactive CD8 and CD4 induced regulatory T cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Adoptive natural regulatory T cell (nTreg) therapy has improved the outcome for patients suffering from graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT). However, fear of broad immune suppression and subsequent dampening of beneficial graft-versus-leukemic (GVL) responses remains a challenge. To address this concern, we generated alloreactive induced Tregs (iTregs) from resting CD4 or CD8 T cells and tested their ability to suppress GVH and maintain GVL responses. We utilized major mismatched and haploidentical murine models of HCT with host-derived lymphoma or leukemia cell lines to evaluate GVH and GVL responses simultaneously. Alloreactive CD4 iTregs were effective in preventing GVHD, but abrogated the GVL effect against aggressive leukemia. Alloreactive CD8 iTregs moderately attenuated GVHD while sparing the GVL effect. Hence, we reasoned that using a combination of CD4 and CD8 iTregs could achieve the optimal goal of allo-HCT. Indeed, the combinational therapy was superior to CD4 or CD8 iTreg singular therapy in GVHD control; importantly, the combinational therapy maintained GVL responses. Cellular analysis uncovered potent suppression of both CD4 and CD8 effector T cells by the combinational therapy that resulted in effective prevention of GVHD, which could not be achieved by either singular therapy. Gene expression profiles revealed alloreactive CD8 iTregs possess elevated expression of multiple cytolytic molecules compared to CD4 iTregs, which likely contributes to GVL preservation. Our study uncovers unique differences between alloreactive CD4 and CD8 iTregs that can be harnessed to create an optimal iTreg therapy for GVHD prevention with maintained GVL responses.
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| Overall design |
12 samples analyzed, experimental groups (n=3) were CD8+GFP+ and n=3 CD4+GFP+, with GFP being a reporter for Foxp3 expression; controls (n=3) were CD8+GFP- and CD4+GFP-.
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| Contributor(s) |
Heinrichs J, Li J, Nguyen H, Wu Y, Bastian D, Daethanasanmak A, Sofi M, Schutt S, Liu C, Jin J, Betts B, Anasetti C, Yu X |
| Citation missing |
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| Submission date |
Nov 17, 2015 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Jessica Heinrichs |
| E-mail(s) |
heinric@musc.edu
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| Phone |
813-748-0946
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| Organization name |
Medical University
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| Department |
Microbiology and Immunology
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| Lab |
Xue-Zhong Yu
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| Street address |
86 Johnathan Lucas Street
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| City |
Charleston |
| State/province |
South Carolina |
| ZIP/Postal code |
29425 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA302534 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE75118_RAW.tar |
107.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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