Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 16855607

TLR gateways to CD1 function.

D Branch Moody
View original source ↗Export metadata ↓

Abstract

CD1-restricted T cells can be activated by diverse lipids derived from mammals, bacteria and protozoa. Certain lipids function as antigens, which bind to CD1 proteins and contact T cell antigen receptors. Other lipids activate CD1-restricted T cells by functioning as adjuvants. By stimulating Toll-like receptors on antigen-presenting cells, these adjuvants alter cytokine secretion, lipid antigen synthesis and CD1 protein translation. Delineation of the separate mechanisms by which adjuvants and antigens activate CD1-restricted T cells is leading to new hypotheses about the functions of individual CD1 proteins during the transition from innate to acquired immune responses.

Explore related subjects

Adjuvants, ImmunologicAnimalsAntigen PresentationAntigensAntigens, CD1HumansLipidsLymphocyte ActivationT-LymphocytesToll-Like ReceptorsJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

D Branch Moody. 2006. TLR gateways to CD1 function.. https://doi.org/10.1038/ni1368

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

T cells contribute to lysophosphatidylcholine-induced macrophage activation and demyelination in the CNS.

We have previously shown that intraspinal microinjection of lysophosphatidylcholine (LPC), a potent demyelinating agent, results in a rapid but brief influx of T cells (between 6 and 12 h). This is accompanied by a robust activation of macrophages/microglia that leads to demyelination by 48 h. In the present study, we examined whether this brief influx of T cells contributes to the activation of macrophages/microglia and demyelination by injecting LPC into the dorsal column white matter of athymic Nude mice that lack T cells. We show that there is a significant reduction in macrophage/microglial activation and myelin clearance after LPC injection in Nude mice as compared with wildtype controls. We also show that there is no difference in the recruitment of hematogenous macrophages into the spinal cord after LPC injection in the two mouse strains. Of the T cell cytokines assessed, there was a marked reduction in the mRNA expression of interleukin-2 (IL-2) in Nude mice compared with wildtype animals. Neutralizing IL-2 with function-blocking antibodies in wildtype animals resulted in a significant decrease in the number of phagocytic macrophages/microglia and a reduction in demyelination induced by LPC. While there may be other defects in Nude mice that might contribute to the effects shown here, these data suggest that the brief influx of T cells in this model of chemically-induced demyelination could play a role in macrophage/microglial activation and demyelination. These results may also have implications for remyelination in this and other types of CNS damage.

Adjuvants, Immunologic↗
PubMed2007

fMRI changes in relapsing-remitting multiple sclerosis patients complaining of fatigue after IFNbeta-1a injection.

If fatigue in multiple sclerosis (MS) is related to an abnormal activation of the sensorimotor brain network, the activity of such a network should vary with varying fatigue. We studied 22 patients treated with interferon beta 1a (IFNbeta-1a; Avonex, Biogen, Cambridge, MA) with no fatigue (10) and with reversible fatigue (12). fMRI examinations were performed: 1) the same day of IFNbeta-1a injection (no fatigue; entry), 2) the day after IFNbeta-1a injection (fatigue; time 1), and 3) 4 days after IFNbeta-1a injection (no fatigue; time 2). Patients performed a simple motor task with the right, clinically unaffected hand. At time 1, compared with entry and time 2, MS patients with reversible fatigue showed an increased activation of the thalamus bilaterally. In MS patients without fatigue thalamus was more activated at entry than at time 1. In both groups at entry the primary SMC and the SMA were more activated than at times 1 and 2. At entry and time 1, when compared to patients with reversible fatigue, those without showed increased activations of the SII. Conversely, patients with reversible fatigue had increased activations of the thalamus and of several regions of the frontal lobes. An abnormal recruitment of the fronto-thalamic circuitry is associated with IFNbeta-1a-induced fatigue in MS patients.

Adjuvants, Immunologic↗
PubMed2007

Effect of poly(lactic-co-glycolic acid) contact on maturation of murine bone marrow-derived dendritic cells.

Understanding of biomaterial adjuvant effect and its mechanisms is essential for the effective design and selection of appropriate materials for specific applications. We have previously shown that poly(lactic-co-glycolic acid) (PLGA), one of the most commonly studied polymers in tissue engineering, supports an adjuvant effect as measured by enhanced immune response against a co-delivered model antigen, which was dependent on the form of the biomaterial. Furthermore, we have shown that PLGA induces the maturation of human peripheral blood mononuclear cell-derived dendritic cells (DCs) in vitro. In this study, the effect of PLGA contact on the maturation of murine bone marrow-derived DCs was investigated in part to explain the biomaterial adjuvant effect observed. Treatment of bone marrow-derived DCs from C57BL6 mice with PLGA microparticles or films lead to maturation of these cells as exemplified by increased expression of co-stimulatory molecules CD80 and CD86 and production of proinflammatory cytokines TNF-alpha and IL-6. These results suggest that PLGA contact induces maturation of murine DCs, supporting our observations with human DCs. With the techniques developed in this study and given the results, our future goal is to utilize transgenic murine models to delineate the mechanisms of biomaterial-induced DC maturation.

Adjuvants, Immunologic↗