Human γδ T cell Recognition of lipid A is predominately presented by CD1b or CD1c on dendritic cells
Copyright policy )Human γδ T cell Recognition of lipid A is predominately presented by CD1b or CD1c on dendritic cells
AbstractBackgroundThe γδ T cells serve as early immune defense against certain encountered microbes. Only a few γδ T cell-recognized ligands from microbial antigens have been identified so far and the mechanisms by which γδ T cells recognize these ligands remain unknown. Here we explored the mechanism of interaction of human γδ T cells in peripheral blood with Lipid A (LA).ResultsFirst, resting γδ T cells (mainly Vδ2 T cells) displayed a strong proliferative response to LA-pulsed monocyte-derived dendritic cells (moDC) and LA-pulsed paraformaldehyde-fixed moDC, but not to free LA in a TCR γδ-dependent manner. Second, anti-CD1b or anti-CD1c antibodies could block proliferative response of resting γδ T cells to LA-loaded moDC. Besides, only LA-loaded CD1b/CD1c-transfected C1R lymphoblastoma cells (CD1b-/CD1c-C1R) were able to stimulate the proliferation of human γδ T cells. Third, the expressions of both Toll-like receptor (TLR)2 and TLR4 on surface of LA-activated γδ T cells were upregulated, whereas only anti-TLR4 antibody could partially block their response to LA; Finally LA-loaded moDCs induce γδ T cells to produce Th1 cytokines, such as IFN-γ.ConclusionTaken together, we found a novel mechanism that human γδ T cells recognize LA in a CD1b- or CD1c-restricted manner in first response against Gram-bacteria, while the interaction between TLR4 on γδ T cells and LA might strengthen the subsequent response of γδ T cells.ReviewersThis article was reviewed by Hao Shen, Youwen He (nominated by Dr. Laurence C Eisenlohr), Dr. Michael Lenardo and Dr. Pushpa Pandiyan.
- Chinese Academy of Medical Sciences & Peking Union Medical College China (People's Republic of)
- PEKING UNION MEDICAL COLLEGE China (People's Republic of)
- Thomas Jefferson University United States
- Duke University Medical Center United States
- Thomas Jefferson University
Antigen Presentation, Agricultural and Biological Sciences(all), QH301-705.5, Biochemistry, Genetics and Molecular Biology(all), Research, Models, Immunological, Receptors, Antigen, T-Cell, gamma-delta, Dendritic Cells, In Vitro Techniques, Th1 Cells, Lymphocyte Activation, Monocytes, Toll-Like Receptor 2, Antigens, CD1, Toll-Like Receptor 4, Lipid A, T-Lymphocyte Subsets, Cytokines, Humans, Biology (General), Cell Proliferation, Glycoproteins
Antigen Presentation, Agricultural and Biological Sciences(all), QH301-705.5, Biochemistry, Genetics and Molecular Biology(all), Research, Models, Immunological, Receptors, Antigen, T-Cell, gamma-delta, Dendritic Cells, In Vitro Techniques, Th1 Cells, Lymphocyte Activation, Monocytes, Toll-Like Receptor 2, Antigens, CD1, Toll-Like Receptor 4, Lipid A, T-Lymphocyte Subsets, Cytokines, Humans, Biology (General), Cell Proliferation, Glycoproteins
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