Purpose The goal of this work is to provide a large and consistent set of data for detector‐specific output correction factors, kQitalicclin,Qitalicref0.166667emfitalicclin,fref, for small static fields for seven solid‐state detectors and to determine field output factors, ΩQitalicclin,Qitalicreffclin,fref, using EBT3 radiochromic films and W1 plastic scintillator as reference detectors on two different linear accelerators and four megavoltage photon beams. Consistent measurement conditions and recommendations given in the International Code of Practice TRS‐483 for small‐field dosimetry were followed throughout the study. Methods ΩQitalicclin,Qitalicreffclin,fref were determined on two linacs, Elekta Versa HD and Varian TrueBeam, for 6 and 10 MV beams with and without flattening filter and for nine fields ranging from 0.5 × 0.5 cm2 to 10 × 10 cm2. Signal readings obtained with EBT3 radiochromic films and W1 plastic scintillator were fitted by an analytical function. Volume averaging correction factors, determined from two‐dimensional (2D) dose matrices obtained with EBT3 films and fitted to bivariate Gaussian function, were used to correct measured signals. kQitalicclin,Qitalicreffclin,fref were determined empirically for six diodes, IBA SFD, IBA Razor, PTW 60008 P, PTW 60012 E, PTW 60018 SRS, and SN EDGE, and a PTW 60019 microDiamond detector. Results Field output factors and detector‐specific kQitalicclin,Qitalicreffclin,fref are presented in the form of analytical functions as well as in the form of discrete values. It is found that in general, for a given linac, small‐field output factors need to be determined for every combination of beam energy and filtration (WFF or FFF) and field size as the differences between them can be statistically significant (P < 0.05). For different beam energies, the present data for kQitalicclin,Qitalicreffclin,fref are found to differ significantly (P < 0.05) from the corresponding data published in TRS‐483 mostly for the smallest fields (<1.5 cm). For the PTW microDiamond detector, statistically significant differences (P < 0.05) between kQitalicclin,Qitalicreffclin,fref values were found for all investigated beams on an Elekta Versa HD linac for field sizes 0.5 × 0.5 cm2 and 0.8 × 0.8 cm2. Significant differences in kQitalicclin,Qitalicreffclin,fref between beams of a given energy but with and without flattening filters are found for measurements made in small fields (<1.5 cm) at a given linac. Differences in kQitalicclin,Qitalicreffclin,fref are also found when measurements are made at different linacs using the same beam energy filtration combination; for the PTW microDiamond detector, these differences were found to be around 6% and were considered as significant. Conclusions Selection of two reference detectors, EBT3 films and W1 plastic scintillator, and use of an analytical function, is a novel approach for the determination of ΩQitalicclin,Qitalicreffclin,fref for small static fields in megavoltage photon beams. Large set of kQitalicclin,Qitalicreffclin,fref data for s...

NKG2D is a potent activating receptor that is expressed on cytotoxic immune cells such as CD8 T and NK cells, where it promotes cytotoxicity after binding stress ligands on infected or transformed cells. On NK cell precursors NKG2D modulates proliferation and maturation. Previously, we observed that NKG2D deficiency affects peripheral B cell numbers. In this study, we show that NKG2D regulates B1a cell development and function. We find that mice deficient for NKG2D have a strong reduction of B1a cell numbers. As a result, NKG2D-deficient mice produce significantly less Ag-specific IgM Abs upon immunization with T cell–independent Ags, and they are more susceptible to Gram-negative sepsis. Klrk1−/− B1a cells are also functionally impaired and they fail to provide protection against Francisella novicida upon adoptive transfer. Using mixed bone marrow chimeric mice, we show that the impact of NKG2D deficiency on B1a cell development is cell intrinsic. No changes in homeostatic turnover and homing of B cells were detectable, limiting the effects of NKG2D to modulation of the hematopoietic development of B1a cells. Using conditional ablation, we demonstrate that the effect of NKG2D on B1a cell development occurs at a developmental stage that precedes the common lymphoid progenitor. Our findings reveal an unexpected new role for NKG2D in the regulation of B1a cell development. The protective effects of this activating receptor therefore reach beyond that of cytotoxic cells, stimulating the immune system to fight bacterial infections by promoting development of innate-like B cells.

The goal of the present work was to provide a large set of detector-specific output correction factors for seven small volume ionization chambers on two linear accelerators in four megavoltage photon beams utilizing perpendicular and parallel orientation of ionization chambers in the beam for nominal field sizes ranging from 0.5 cm 2 9 0.5 cm 2 to 10 cm 2 9 10 cm 2. The present study is the second part of an extensive research conducted by our group. Methods: Output correction factors k f clin ;f ref Q clin ;Q ref were experimentally determined on two linacs, Elekta Versa HD and Varian TrueBeam for 6 and 10 MV beams with and without flattening filter for nine square fields ranging from 0.5 cm 2 9 0.5 cm 2 to 10 cm 2 9 10 cm 2 , for seven mini and micro ionization chambers, IBA CC04, IBA Razor, PTW 31016 3D PinPoint, PTW 31021 3D Semiflex, PTW 31022 3D PinPoint, PTW 31023 PinPoint, and SI Exradin A16. An Exradin W1 plastic scintillator and EBT3 radiochromic films were used as the reference detectors. Results: For all ionization chambers, values of output correction factors k f clin ;f ref Q clin ;Q ref were lower for parallel orientation compared to those obtained in the perpendicular orientation. Five ionization chambers from our study set, IBA Razor, PTW 31016 3D PinPoint, PTW 31022 3D PinPoint, PTW 31023 PinPoint, and SI Exradin A16, fulfill the requirement recommended in the TRS-483 Code of Practice, that is, 0:95\k

The development of a vaccine against human cytomegalovirus (CMV) has been a subject of long-term medical interest. The research during recent years identified CMV as an attractive vaccine vector against infectious diseases and tumors. The immune response to CMV persists over a lifetime and its unique feature is the inflationary T cell response to certain viral epitopes. CMV encodes numerous genes involved in immunoevasion, which are non-essential for virus growth in vitro. The deletion of those genes results in virus attenuation in vivo, which enables us to dramatically manipulate its virulence and the immune response. We have previously shown that the murine CMV (MCMV) expressing RAE-1γ, one of the cellular ligands for the NKG2D receptor, is highly attenuated in vivo but retains the ability to induce a strong CD8+ T cell response. Here, we demonstrate that recombinant MCMV expressing high affinity NKG2D ligand murine UL16 binding protein-like transcript (MULT-1) (MULT-1MCMV) inserted in the place of its viral inhibitor is dramatically attenuated in vivo in a NK cell-dependent manner, both in immunocompetent adult mice and in immunologically immature newborns. MULT-1MCMV was more attenuated than the recombinant virus expressing RAE-1γ. Despite the drastic sensitivity to innate immune control, MULT-1MCMV induced an efficient CD8+ T cell response to viral and vectored antigens. By using in vitro assay, we showed that similar to RAE-1γMCMV, MULT-1 expressing virus provided strong priming of CD8+ T cells. Moreover, MULT-1MCMV was able to induce anti-viral antibodies, which after passing the transplacental barrier protect offspring of immunized mothers from challenge infection. Altogether, this study further supports the concept that CMV expressing NKG2D ligand possesses excellent characteristics to serve as a vaccine or vaccine vector.

Natural killer group 2 member D (NKG2D) is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ, and CD8 T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8 T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here, we studied the impact of NKG2D on effector CD8 T-cell formation. NKG2D deficiency that is restricted to murine CD8 T cells did not impair antigen-specific T-cell expansion following mouse CMV and lymphocytic choriomeningitis virus infection, but reduced their capacity to produce cytokines. Upon infection, conventional dendritic cells induce NKG2D ligands, which drive cytokine production on CD8 T cells via the Dap10 signaling pathway. T-cell development, homing, and proliferation were not affected by NKG2D deficiency and cytotoxicity was only impaired when strong T-cell receptor (TCR) stimuli were used. Transfer of antigen-specific CD8 T cells demonstrated that NKG2D deficiency attenuated their capacity to reduce viral loads. The inability of NKG2D-deficient cells to produce cytokines could be overcome with injection of IL-15 superagonist during priming. In summary, our data show that NKG2D has a nonredundant role in priming of CD8 T cells to produce antiviral cytokines.