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


RESULTS
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.


CONCLUSIONS
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.


METHODS
This article was reviewed by Hao Shen, Youwen He (nominated by Dr. Laurence C Eisenlohr), Dr. Michael Lenardo and Dr. Pushpa Pandiyan.
Cui
Yongchun
Y
Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China. cych2005@yahoo.com.cn
Kang
Lei
L
Cui
Lianxian
L
He
Wei
W
D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000378:metabolism*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008050:Lipid A / Q000276:immunology*; D008213:Lymphocyte Activation; D018448:Models, Immunological; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D018949:Antigens, CD1; C437944:CD1C protein, human; C419394:CD1b antigen; D016207:Cytokines; D006023:Glycoproteins; D008050:Lipid A; D016692:Receptors, Antigen, T-Cell, gamma-delta; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4