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

Yongchun Cui,Lianxian Cui,Lei Kang,Wei He

doi:10.1186/1745-6150-4-47

Yongchun Cui, Lianxian Cui + Show 2 more

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https://doi.org/10.1186/1745-6150-4-47

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Abstract

BackgroundThe 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.

Highlights

The γδ T cells serve as early immune defense against certain encountered microbes
IL-2 with or without Lipid A (LA) induced a modest expansion of γδ T cells, when monocyte-derived dendritic cells (moDC) were excluded in the culture (Fig. 2A), suggesting that LA can induce significant expansion of γδ T cells in the presence of autologous moDC
In CFSE dilution assay, no matter using γδ T cell-enriched PBMC (Fig. 2D) or purified γδ T cell (Fig. 3), γδ T cells proliferated significantly after stimulated with LA plus IL-2 in the presence of moDCs. These results strongly suggest that LA-pulsed moDC induced human γδ T cell proliferation

Summary

Introduction

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. We explored the mechanism of interaction of human γδ T cells in peripheral blood with Lipid A (LA). Many studies demonstrated that TCRγδ+ T cells could have a sentinel role in the early host response against parasitic [1], bacterial [2] and viral infections [3]. Γδ T cells can recognize non-peptide molecules, such as microbial metabolites (pyrophosphomonoesters and alkyl amines) [4,5] and synthetic aminobisphosphonates (pamidronate) [6] directly via TCRγδ. Several studies demonstrated that the interaction of T cells with lipid/glycolipid antigens is associated with MHC-like cluster of differentiation (CD) molecules [7,8], most such (page number not for citation purposes). The mechanism of human γδ T cells recognizing lipid antigens is largely unknown

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