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BACKGROUND: Environmental contamination by fluorinated chemicals, in particular chemicals from the per- and polyfluoroalkyl substances (PFAS) class, has raised concerns around the globe because of documented adverse impacts on human health, wildlife, and ecosystem quality. Recent studies have indicated that pesticide products may contain a variety of chemicals that meet the PFAS definition, including the active pesticide ingredients themselves. Given that pesticides are some of the most widely distributed pollutants across the world, the legacy impacts of PFAS addition into pesticide products could be widespread and have wide-ranging implications on agriculture and food and water contamination, as well as the presence of PFAS in rural environments. OBJECTIVES: The purpose of this commentary is to explore different ways that PFAS can be introduced into pesticide products, the extent of PFAS contamination of pesticide products, and the implications this could have for human and environmental health. METHODS: We submitted multiple public records requests to state and federal agencies in the United States and Canada and extracted relevant data from those records. We also compiled data from publicly accessible databases for our analyses. DISCUSSION: We found that the biggest contributor to PFAS in pesticide products was active ingredients and their degradates. Nearly a quarter of all US conventional pesticide active ingredients were organofluorines and 14% were PFAS, and for active ingredients approved in the last 10 y, this had increased to 61% organofluorines and 30% PFAS. Another major contributing source was through PFAS leaching from fluorinated containers into pesticide products. Fluorination of adjuvant products and "inert" ingredients appeared to be limited, although this represents a major knowledge gap. We explored aspects of immunotoxicity, persistence, water contamination, and total fluorine load in the environment and conclude that the recent trend of using fluorinated active ingredients in pesticides may be having effects on chemical toxicity and persistence that are not given adequate oversight in the United States. We recommend a more stringent risk assessment approach for fluorinated pesticides, transparent disclosure of "inert" ingredients on pesticide labels, a complete phase-out of post-mold fluorination of plastic containers, and greater monitoring in the United States. https://doi.org/10.1289/EHP13954, Introduction Pesticides are commonly used in the United States and around the world to kill or suppress certain organisms on farmland and in areas where people live and work. Although [...]

We have purified soluble mouse and human CD1d molecules to assess the structural requirements for lipid antigen presentation by CD1. Plate-bound CD1d molecules from either species can present the glycolipid alpha-galactosyl ceramide (alpha-GalCer) to mouse natural killer T cells, formally demonstrating both the in vitro formation of antigenic complexes, and the presentation of alpha-GalCer by these two CD1d molecules. Using surface plasmon resonance, we show that at neutral pH, mouse CD1 and human CD1d bind to immobilized alpha-GalCer, unlike human CD1b, which requires acidic pH for lipid antigen binding. The CD1d molecules can also bind both to the nonantigenic beta-GalCer and to phosphatidylethanolamine, indicating that diverse lipids can bind to CD1d. These studies provide the first quantitative analysis of monomeric lipid antigen-CD1 interactions, and they demonstrate that the orientation of the galactose, or even the nature of the polar head group, are likely to be more important for T cell receptor contact than CD1d binding.

Background: New research has attributed increased significance to the causal link between ultraviolet A (UVA) radiation and immunosuppression and carcinogenesis. In the United States, sunscreens are labeled with only their sun protection factor (SPF) and an imprecise term "broad‐spectrum protection." Sunscreen marketing and efficacy evaluations continue to be based primarily on skin redness (sunburn) or erythema. We sought to evaluate the ultraviolet (UV) protection offered by common sunscreen products on the US market using laboratory‐measured UV‐absorption testing and comparing with computer‐modeled protection and the labeled SPF values. This approach enables an investigation of the relationship between the labeled SPF and measured UVA protection, a factor that is ignored in current regulations. Methods: Fifty‐one sunscreen products for sale in the United States with SPF values from 15 to 110 and labeled as providing broad‐spectrum protection were tested using a commercial laboratory. All products were evaluated using the ISO 24443:2012 method for sunscreen effectiveness. The final absorbance spectra were used for analysis of in vitro UV protection. Results: In vitro SPF values from laboratory‐measured UV absorption and computer modeling were on average just 59 and 42 percent of the labeled SPF. The majority of products provided significantly lower UVA protection with the average unweighted UVA protection factor just 24 percent of the labeled SPF. Conclusion: Regulations and marketplace forces promote sunscreens that reduce sunburn instead of products that provide better, more broad‐spectrum UV protection. The production and use of products with broad spectrum UV protection should be incentivized, removing the emphasis on sunburn protection and ending testing on people. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells express inhibitory and activation receptors that recognize MHC class I-like molecules on target cells. These receptors may be involved in the critical role of NK cells in controlling initial phases of certain viral infections. Indeed, the Ly49H NK cell activation receptor confers in vivo genetic resistance to murine cytomegalovirus (MCMV) infections, but its ligand was previously unknown. Herein, we use heterologous reporter cells to demonstrate that Ly49H recognizes MCMV-infected cells and a ligand encoded by MCMV itself. Exploiting a bioinformatics approach to the MCMV genome, we find at least 11 ORFs for molecules with previously unrecognized features of predicted MHC-like folds and limited MHC sequence homology. We identify one of these, m157, as the ligand for Ly49H. m157 triggers Ly49H-mediated cytotoxicity, and cytokine and chemokine production by freshly isolated NK cells. We hypothesize that the other ORFs with predicted MHC-like folds may be involved in immune evasion or interactions with other NK cell receptors.

The thymus leukemia antigen (TL) is a nonclassical class I molecule, expressed abundantly on intestinal epithelial cells. We show that, in contrast to other major histocompatibility complex (MHC) class I molecules that bind CD8αβ, TL preferentially binds the homotypic form of CD8α (CD8αα). Thus, TL tetramers react specifically to CD8αα-expressing cells, including most intestinal intraepithelial lymphocytes. Compared with CD8αβ, which recognizes the same HHC as the T cell receptor (TCR) and thus acts as a TCR coreceptor, high-affinity binding of CD8αα to TL modifies responses mediated by TCR recognition of antigen presented by distinct MHC molecules. These findings define a novel mechanism of lymphocyte regulation through CD8αα and MHC class I., Several nonclassical class I molecules are encoded in the T region of the mouse MHC. These proteins are antigens and are named after the thymus leukemia antigen (TL) encoded by [...]

Type 1 diabetes (T1D) in non-obese diabetic (NOD) mice may be favored by immune dysregulation leading to the hyporesponsiveness of regulatory T cells and activation of effector T-helper type 1 (Th1) cells. The immunoregulatory activity of natural killer T (NKT) cells is well documented, and both interleukin (IL)-4 and IL-10 secreted by NKT cells have important roles in mediating this activity. NKT cells are less frequent and display deficient IL-4 responses in both NOD mice and individuals at risk for T1D (ref. 8), and this deficiency may lead to T1D (refs. 1,6-9). Thus, given that NKT cells respond to the [alpha]-galactosylceramide ([alpha]-GalCer) glycolipid in a CD1d-restricted manner by secretion of Th2 cytokines, we reasoned that activation of NKT cells by [alpha]-GalCer might prevent the onset and/or recurrence of T1D. Here we show that [alpha]-GalCer treatment, even when initiated after the onset of insulitis, protects female NOD mice from T1D and prolongs the survival of pancreatic islets transplanted into newly diabetic NOD mice. In addition, when administered after the onset of insulitis, [alpha]-GalCer and IL-7 displayed synergistic effects, possibly via the ability of IL-7 to render NKT cells fully responsive to [alpha]-GalCer. Protection from T1D by [alpha]-GalCer was associated with the suppression of both T- and B-cell autoimmunity to islet [beta] cells and with a polarized Th2-like response in spleen and pancreas of these mice. These findings raise the possibility that[alpha]-GalCer treatment might be used therapeutically to prevent the onset and recurrence of human T1D., Author(s): Shayan Sharif [1, 9]; Guillermo A. Arreaza [1, 9]; Peter Zucker [1, 9]; Qing-Sheng Mi [1, 9]; Jitin Sondhi [1, 9]; Olga V. Naidenko [2, 9]; Mitchell Kronenberg [2, [...]

Diabetes in non-obese diabetic (NOD) mice is mediated by pathogenic T-helper type 1 (Th1) cells that arise because of a deficiency in regulatory or suppressor T cells. V[alpha]14-J[alpha]15 natural killer T (NKT) cells recognize lipid antigens presented by the major histocompatibility complex class I-like protein CD1d (refs. 3,4). We have previously shown that in vivo activation of V[alpha]14 NKT cells by [alpha]-galactosylceramide ([alpha]-GalCer) and CD1d potentiates Th2-mediated adaptive immune responses. Here we show that [alpha]-GalCer prevents development of diabetes in wild-type but not CD1d-deficient NOD mice. Disease prevention correlated with the ability of [alpha]-GalCer to suppress interferon-[gamma] but not interleukin-4 production by NKT cells, to increase serum immunoglobulin E levels, and to promote the generation of islet autoantigen-specific Th2 cells. Because [alpha]-GalCer recognition by NKT cells is conserved among mice and humans, these findings indicate that [alpha]-GalCer might be useful for therapeutic intervention in human diseases characterized by Th1-mediated pathology such as Type 1 diabetes., Author(s): Seokmann Hong [1, 5]; Michael T. Wilson [1, 5]; Isao Serizawa [2, 5]; Lan Wu [3]; Nagendra Singh [1]; Olga V. Naidenko [4]; Toru Miura [2]; Tomoku Haba [2]; [...]