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Biology direct

Human gammadelta T cell recognition of lipid A is predominately presented by CD1b or CD1c on dendritic cells.


PMID 19948070

Abstract

The gammadelta T cells serve as early immune defense against certain encountered microbes. Only a few gammadelta T cell-recognized ligands from microbial antigens have been identified so far and the mechanisms by which gammadelta T cells recognize these ligands remain unknown. Here we explored the mechanism of interaction of human gammadelta T cells in peripheral blood with Lipid A (LA). First, resting gammadelta T cells (mainly Vdelta2 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 gammadelta-dependent manner. Second, anti-CD1b or anti-CD1c antibodies could block proliferative response of resting gammadelta 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 gammadelta T cells. Third, the expressions of both Toll-like receptor (TLR)2 and TLR4 on surface of LA-activated gammadelta T cells were upregulated, whereas only anti-TLR4 antibody could partially block their response to LA; Finally LA-loaded moDCs induce gammadelta T cells to produce Th1 cytokines, such as IFN-gamma. Taken together, we found a novel mechanism that human gammadelta T cells recognize LA in a CD1b- or CD1c-restricted manner in first response against Gram-bacteria, while the interaction between TLR4 on gammadelta T cells and LA might strengthen the subsequent response of gammadelta T cells. This article was reviewed by Hao Shen, Youwen He (nominated by Dr. Laurence C Eisenlohr), Dr. Michael Lenardo and Dr. Pushpa Pandiyan.