New approaches to eliciting protective immunity through T cell repertoire manipulation: the concept of thymic vaccination

Conventional vaccines afford protection against infectious diseases by expanding existing pathogen-specific peripheral lymphocytes, both CD8 cytotoxic effector (CTL) and CD4 helper T cells. The latter induce B cell maturation and antibody production. As a consequence, lymphocytes within the memory pool are poised to rapidly proliferate at the time of a subsequent infection. The "thymic vaccination" concept offers a novel way to alter the primary T cell repertoire through exposure of thymocytes to altered peptide ligands (APL) with reduced T cell receptor (TCR) affinity relative to cognate antigens recognized by those same TCRs. Thymocyte maturation (i.e. positive selection) is enhanced by low affinity interaction between a TCR and an MHC-bound peptide in the thymus and subsequent emigration of mature cells into the peripheral T lymphocyte pool follows. In principal, such variants of antigens derived from infectious agents could be utilized for peptide-driven maturation of thymocytes bearing pathogen-specific TCRs. To test this idea, APLs of gp33-41, a Db-restricted peptide derived from the lymphocytic choriomeningitis virus (LCMV) glycoprotein, and of VSV8, a Kb-restricted peptide from the vesicular stomatitis virus (VSV) nucleoprotein, have been designed and their influence on thymic maturation of specific TCR-bearing transgenic thymocytes examined in vivo using irradiation chimeras. Injection of APL resulted in positive selection of CD8 T cells expressing the relevant viral specificity and in the export of those virus-specific CTL to lymph nodes without inducing T cell proliferation. Thus, exogenous APL administration offers the potential of expanding repertoires in vivo in a manner useful to the organism. To efficiently peripheralize antigen-specific T cells, concomitant enhancement of mechanisms promoting thymocyte migration appears to be required. This commentary describes the rationale for thymic vaccination and addresses the potential prophylactic and therapeutic applications of this approach for treatment of infectious diseases and cancer. Thymic vaccination-induced peptide-specific T cells might generate effective immune protection against disease-causing agents, including those for which no effective natural protection exists.     

Religious visibility: perceptions and experiences of residents in two Muslim concentration suburbs in Melbourne,Australia

In recent decades, and especially after the 9/11/2001 terrorist attack on US, an antipathy towards and fear of Muslim minorities in Western countries have increased, forming part of the current widespread anti-immigration sentiment. In this context, the ‘religiously visible’ Muslims are the most obvious target of negative perceptions, discrimination and other manifestations of ‘Islamophobia’. This paper uses quantitative and qualitative data on religious visibility collected through a survey and in-depth interviews in two suburbs with residential concentrations of Muslims in Melbourne, Australia. The two localities, ‘Broadburb’ and ‘Greenburb’, have similar proportions of Muslim residents (about 1/3) but the levels of religious visibility differ. The paper discusses perceptions and experiences of being religiously visible in a secular society, and particularly being a ‘visible Muslim’. We also discuss perceptions of Muslim visibility by others – non-visible Muslims and non-Muslims – who share neighbourhoods with the visible Muslim minority.     

Use of thermal and visible imagery for estimating crop water status of irrigated grapevine

Achieving high quality wine grapes depends on the ability to maintain mild to moderate levels of water stress in the crop during the growing season. This study investigates the use of thermal imaging for monitoring water stress. Experiments were conducted on a wine-grape (Vitis vinifera cv. Merlot) vineyard in northern Israel. Irrigation treatments included mild, moderate, and severe stress. Thermal and visible (RGB) images of the crop were taken on four days at midday with a FLIR thermal imaging system and a digital camera, respectively, both mounted on a truck-crane 15 m above the canopy. Aluminium crosses were used to match visible and thermal images in post-processing and an artificial wet surface was used to estimate the reference wet temperature (T(wet)). Monitored crop parameters included stem water potential (Psi(stem)), leaf conductance (g(L)), and leaf area index (LAI). Meteorological parameters were measured at 2 m height. CWSI was highly correlated with g(L) and moderately correlated with Psi(stem). The CWSI-g(L) relationship was very stable throughout the season, but for that of CWSI-Psi(stem) both intercept and slope varied considerably. The latter presumably reflects the non-direct nature of the physiological relationship between CWSI and Psi(stem). The highest R(2) for the CWSI to g(L) relationship, 0.91 (n=12), was obtained when CWSI was computed using temperatures from the centre of the canopy, T(wet) from the artificial wet surface, and reference dry temperature from air temperature plus 5 degrees C. Using T(wet) calculated from the inverted Penman-Monteith equation and estimated from an artificially wetted part of the canopy also yielded crop water-stress estimates highly correlated with g(L) (R(2)=0.89 and 0.82, respectively), while a crop water-stress index using 'theoretical' reference temperatures computed from climate data showed significant deviations in the late season. Parameter variability and robustness of the different CWSI estimates are discussed. Future research should aim at developing thermal imaging into an irrigation scheduling tool applicable to different crops.     

The peptide-binding activity of GRP94 is regulated by calcium

GRP94 (glucose-regulated protein of 94 kDa) is a major luminal constituent of the endoplasmic reticulum with known high capacity for calcium in vivo and a peptide-binding activity in vitro. In the present study, we show that Ca2+ regulates the ability of GRP94 to bind peptides. This effect is due to a Ca2+-binding site located in the charged linker domain of GRP94, which, when occupied, enhances the association of peptides with the peptide-binding site in the N-terminal domain of the protein. We further show that grp94-/- cells are hypersensitive to perturbation of intracellular calcium and thus GRP94 is important for cellular Ca2+ storage.     

GRP94 is essential for mesoderm induction and muscle development because it regulates insulin-like growth factor secretion

Because only few of its client proteins are known, the physiological roles of the endoplasmic reticulum chaperone glucose-regulated protein 94 (GRP94) are poorly understood. Using targeted disruption of the murine GRP94 gene, we show that it has essential functions in embryonic development. grp94-/- embryos die on day 7 of gestation, fail to develop mesoderm, primitive streak, or proamniotic cavity. grp94-/- ES cells grow in culture and are capable of differentiation into cells representing all three germ layers. However, these cells do not differentiate into cardiac, smooth, or skeletal muscle. Differentiation cultures of mutant ES cells are deficient in secretion of insulin-like growth factor II and their defect can be complemented with exogenous insulin-like growth factors I or II. The data identify insulin-like growth factor II as one developmentally important protein whose production depends on the activity of GRP94.