Utilizing the adjuvant properties of CD1d-dependent NK T cells in T cell-mediated immunotherapy.
J Clin Invest 114:12 (2004) 1800-1811
Abstract:
Activation of invariant CD1d-dependent NK T cells (iNKT cells) in vivo through administration of the glycolipid ligand alpha-galactosylceramide (alpha-GalCer) or the sphingosine-truncated alpha-GalCer analog OCH leads to CD40 signaling as well as the release of soluble molecules including type 1 and gamma interferons that contribute to DC maturation. This process enhances T cell immunity to antigens presented by the DC. The adjuvant activity is further amplified if APCs are stimulated through Toll-like receptor 4, suggesting that iNKT cell signals can amplify maturation induced by microbial stimuli. The adjuvant activity of alpha-GalCer enhances both priming and boosting of CD8(+) T cells to coadministered peptide or protein antigens, including a peptide encoding the clinically relevant, HLA-A2-restricted epitope of the human tumor antigen NY-ESO-1. Importantly, alpha-GalCer was used to induce CD8(+) T cells to antigens delivered orally, despite the fact that this route of administration is normally associated with blunted responses. Only T cell responses induced in the presence of iNKT cell stimulation, whether by the i.v. or oral route, were capable of eradicating established tumors. Together these data highlight the therapeutic potential of iNKT cell ligands in vaccination strategies, particularly "heterologous prime-boost" strategies against tumors, and provide evidence that iNKT cell stimulation may be exploited in the development of oral vaccines.Determining Foreground Contamination in CMB Observations: Diffuse Galactic Emission in the MAXIMA-I Field
Astrophys.J. 615 (2004) 55-62
Abstract:
Observations of the CMB can be contaminated by diffuse foreground emission from sources such as Galactic dust and synchrotron radiation. In these cases, the morphology of the contaminating source is known from observations at different frequencies, but not its amplitude at the frequency of interest for the CMB. We develop a technique for accounting for the effects of such emission in this case, and for simultaneously estimating the foreground amplitude in the CMB observations. We apply the technique to CMB data from the MAXIMA-1 experiment, using maps of Galactic dust emission from combinations of IRAS and DIRBE observations, as well as compilations of Galactic synchrotron emission observations. The spectrum of the dust emission over the 150--450 GHz observed by MAXIMA is consistent with preferred models but the effect on CMB power spectrum observations is negligible.Determining foreground contamination in cosmic microwave background observations: Diffuse galactic emission in the MAXIMA-I field
Astrophysical Journal 615:1 I (2004) 55-62
Abstract:
Observations of the cosmic microwave background (CMB) can be contaminated by diffuse foreground emission from sources such as Galactic dust and synchrotron radiation. In these cases, the morphology of the contaminating source is known from observations at different frequencies, but not its amplitude at the frequency of interest for the CMB. We develop a technique for accounting for the effects of such emission in this case, and for simultaneously estimating the foreground amplitude in the CMB observations. We apply the technique to CMB data from the MAXIMA-1 experiment, using maps of Galactic dust emission from combinations of IRAS and DIRBE observations, as well as compilations of Galactic synchrotron emission observations. The spectrum of the dust emission over the 150-450 GHz observed by MAXIMA is consistent with preferred models, but the effect on CMB power spectrum observations is negligible.Constraints on isocurvature models from the WMAP first-year data
Physical Review D 70 (2004) 103520 20pp