Characterization of Human CD8(+)TCR(-) Facilitating Cells In Vitro and In Vivo in a NOD/SCID/IL2rγ(null) Mouse Model.

CD8(+)/TCR(-) facilitating cells (FCs) in mouse bone marrow (BM) significantly enhance engraftment of hematopoietic stem/progenitor cells (HSPCs). Human FC phenotype and mechanism of action remain to be defined. We report, for the first time, the phenotypic characterization of human FCs and correlation of phenotype with function. Approximately half of human FCs are CD8(+)/TCR(-)/CD56 negative (CD56(neg)); the remainder are CD8(+)/TCR(-)/CD56 bright (CD56(bright)). The CD56(neg) FC subpopulation significantly promotes homing of HSPCs to BM in nonobese diabetic/severe combined immunodeficiency/IL-2 receptor γ-chain knockout mouse recipients and enhances hematopoietic colony formation in vitro. The CD56(neg) FC subpopulation promotes rapid reconstitution of donor HSPCs without graft-versus-host disease (GVHD); recipients of CD56(bright) FCs plus HSPCs exhibit low donor chimerism early after transplantation, but the level of chimerism significantly increases with time. Recipients of HSPCs plus CD56(neg) or CD56(bright) FCs showed durable donor chimerism at significantly higher levels in BM. The majority of both FC subpopulations express CXCR4. Coculture of CD56(bright) FCs with HSPCs upregulates cathelicidin and ß-defensin 2, factors that prime responsiveness of HSPCs to stromal cell-derived factor 1. Both FC subpopulations significantly upregulated mRNA expression of the HSPC growth factors and Flt3 ligand. These results indicate that human FCs exert a direct effect on HSPCs to enhance engraftment. Human FCs offer a potential regulatory cell-based therapy for enhancement of engraftment and prevention of GVHD.

An inventory of human exposure-related data bases.

An inventory of Federally-sponsored data bases, which either have been or could be used to estimate human exposures to environmental agents, was compiled through a joint effort by the Environmental Protection Agency (EPA), the National Center for Health Statistics (CDC-NCHS), and the Agency for Toxic Substances and Disease Registry (ATSDR). The inventory includes sixty-seven exposure-related data systems that meet the following criteria: cover a relatively large geographical area (e.g., national, state); provide reasonable access to information; and are supported, at least in part, by Federal funds. Findings allow for comparison of data bases according to 1) exposure estimators (e.g., emission estimates, environmental measurements), 2) sample types (e.g., air, water soil, food, human tissue), 3) measured/observed parameters (e.g., pesticides, PCBs, microorganisms), 4) geographic scope (e.g., national, regional, state), 5) sample collection frequency (e.g., yearly, quarterly, daily), and 6) sample location identifiers (e.g., latitude/longitude, zip code, county). Results indicate that existing data bases were established for a variety of reasons (e.g., regulatory compliance, research, monitor environmental conditions, legal requirements) and contain information which varies widely in terms of quality, relevance, and availability. Although the inventory identifies many potential sources of information, it also highlights significant shortcomings in the available systems, including an almost complete absence of data on contact between people and environmental agents (human exposure) and on the amount of the agent that is absorbed into the body (dose).

Role of exposure databases in risk management.

Despite the development of numerous national exposure-related databases, exposure assessment remains a weak link in the chain of risk assessment and risk-management activities. Most databases include measures of environmental releases or concentrations of pollutants in specific media, but do not include actual measures of exposure. If accurate estimates of exposure experienced by populations or individuals are absent, it is impossible to judge the effectiveness of risk-management strategies. The Risk Management Work Group evaluation identified the following needs: refinement of measurements of total exposure experienced by individuals, improved characterization of the distribution of exposures in the population, longitudinal monitoring of exposure trends, and improved information about the public health implications of exposure. Recommendations are presented with the hope that the utility of existing databases will be improved and that future initiatives will be developed that meet the needs of risk management.

A customer's definition of quality.

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