Human γδ T cell Recognition of lipid A is predominately presented by CD1b or CD1c on dendritic cells

BACKGROUND: The 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). RESULTS: First, 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. CONCLUSION: Taken 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. REVIEWERS: This article was reviewed by Hao Shen, Youwen He (nominated by Dr. Laurence C Eisenlohr), Dr. Michael Lenardo and Dr. Pushpa Pandiyan.