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Liver sinusoidal endothelial cell cross-priming is supported by CD4 T cell-derived IL-2
- Source :
- Journal of Hepatology. 66:978-986
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Background & Aims Liver sinusoidal endothelial cells (LSECs) are prominent liver-resident antigen (cross-)presenting cells. LSEC cross-priming of naive CD8 T cells does not require CD4 T cell help in contrast to priming by dendritic cells (DC) but leads to the formation of memory T cells that is preceded by transient Granzyme B (GzmB) expression. Here we provide evidence for a so far unrecognized CD4 T helper cell function in LSEC-induced CD8 T cell activation. Methods Naive CD8 T cells and differentiated T helper 1 (T h 1) cells were stimulated by antigen-presenting LSEC, and GzmB expression in CD8 T cells was determined by flow cytometry. To identify molecular pathways mediating this GzmB expression, mechanistic proof-of-concept experiments were conducted using stimulatory anti-CD3 antibody together with Hyper-IL-6. Results We demonstrate that LSECs simultaneously function in antigen co-presentation to CD8 and CD4 T cells. Such co-presentation revealed a function of T h 1 cells to increase GzmB expression in CD8 T cells after LSEC but not DC cross-priming. IL-2 released from T h 1 cells was required but not sufficient for rapid GzmB induction in CD8 T cells. T cell receptor together with IL-6 trans-signaling was necessary for IL-2 to mediate rapid GzmB induction. Conclusions Our findings indicate that LSECs can serve as a platform to facilitate CD4–CD8 T cell crosstalk enhancing the immune function of LSECs to cross-prime CD8 T cells. IL-6 trans-signaling-mediated responsiveness for IL-2 inducing sustained GzmB expression in CD8 T cells reveals unique mechanisms of CD4 T cell help and CD8 T cell differentiation through liver-resident antigen-presenting cells. Lay summary Our findings demonstrate that LSEC co-present antigen to CD8 and CD4 T cells and thereby enable CD4 T cell help for LSEC-priming of CD8 T cells. This CD4 T cell help selectively enhances the rapid upregulation of GzmB and effector function of LSEC-primed CD8 T cells thereby enhancing functional differentiation towards CD8 effector T cells.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
T cell
Antigen-Presenting Cells
Priming (immunology)
Cell Communication
CD8-Positive T-Lymphocytes
Biology
Granzymes
GZMB
Mice
03 medical and health sciences
Interleukin 21
Cross-Priming
0302 clinical medicine
medicine
Animals
Cytotoxic T cell
Antigen-presenting cell
Cells, Cultured
Hepatology
Endothelial Cells
T helper cell
Natural killer T cell
Cell biology
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Liver
030220 oncology & carcinogenesis
Interleukin-2
Subjects
Details
- ISSN :
- 01688278
- Volume :
- 66
- Database :
- OpenAIRE
- Journal :
- Journal of Hepatology
- Accession number :
- edsair.doi.dedup.....1e4a62a48d374cd541ac33a14efff7ae