Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4+ T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4+ T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4+ T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4+ T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences.
Skin test-active, phenol-soluble, water-soluble (PSWS) extracts of Coccidioides immitis whole, defatted mycelia were compared with skin test-active, alkalisoluble, water-soluble (ASWS) extracts of mycelial cell walls. Both PSWS and ASWS extracts contained partially 3-0-methylated mannan. Composition analysis of both PSWS and ASWS extracts indicated mannose and glucose as major components, whereas 3-0-methylmannose and galactose were minor constituents. These heteromannans and glucans could be obtained from cell walls by extraction with either mild acid or alkali, but not with aqueous phenol. We therefore conclude that the PSWS extracts which were obtainable from whole mycelia but not from cell walls represent cellular (i.e., periplasmic, membrane associated, or cytoplasmic), nonwall polymers. Both PSWS and ASWS mycelial extracts and their gel filtration fractions reacted with rabbit antispherule serum, but with little cross-reactivity. However, alkali treatment of higher-molecularweight PSWS extract polymers yielded products that cross-reacted with serological identity with low-molecular-weight components of ASWS extracts of mycelial walls, indicating that cell walls and cellular polymers share antigenic determinants. Finally, gel filtration of PSWS extracts on Sephacryl S-200 and Sepharose CL 4B yielded fractions that reacted with serological identity with one or more components of mycelial cytosol, mycelial culture filtrate and autolysate coccidioidins, and spherulin.
Delayed hypersensitivity skin tests with mycelium-derived (coccidioidin) or spherule-derived (spherulin) antigens (or both) can be used to identify patients who have been sensitized to the dimorphic fungus Coccidioides immitis. Prior studies suggest that coccidioidin and spherulin skin test antigens detect comparable numbers of reactors among exposed subjects. Studies in subjects residing in areas outside the United States where C. immitis is not endemic suggest that both antigens are specific for the fungus. The specificity and reactivity of coccidioidin and spherulin have not been compared in nonendemic regions of the United States in which the skin test antigens and an appropriate travel or exposure history are used to identify patients with possible C. immitis infection. A review of delayed cutaneous reactions to coccidioidin in 6,375 patients tested between 1970 and 1979 in the southeastern United States revealed 958 (15.0%) and 234 (5.7%) positive reactions (-5 mm), respectively, at 24 and 48 h. Subsequent tests with spherulin in 2,775 patients tested in 1980 and 1981 revealed 866 (31.2%) and 288 (10.3%) positive reactions, respectively, at 24 and 48 h. False-positive immediate hypersensitivity reactions contributed to the large number of spherulin reactors at 24 h. Differences among the patients sampled, work exposure, and travel history were excluded as causes of this surprising and highly significant (P s 0.0001) difference in the 48-h delayed cutaneous reaction. These observations suggest two possibilities: (i) spherulin is less specific than coccidioidin, or (ii) a surprising prevalence of C. immitis sensitization exists among patients in nonendemic regions of the United States.
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