Robert E. Faith

Effect of in utero exposure to diethylstilbestrol on the immune response in mice

The effect of in utero exposure to diethylstilbestrol (DES) on the immune system was investigated. Mice were exposed to DES through maternal dosing (0.1 mg/kg body wt) on Day 16 of gestation. Parameters of cell-mediated and humoral immune function were evaluated between 7 and 9 weeks of age. DES slightly suppressed cellmediated immune function in both males and females. In contrast, a sex specificity was noted in humoral immune function with enhanced antibody responses to a T-independent antigen in males and either no effect or slight suppression in females.

Chemical separation of helper cell function and delayed hypersensitivity responses.

Abstract Studies were performed to investigate the effects of the immunosuppressive chemical TCDD. Fetal and neonatal rats were exposed to TCDD through maternal dosing (5 μg/Kg) at Day 18 of gestation and on Days 0, 7, and 14 of postnatal life. Another group of neonatal rats were exposed to TCDD through maternal dosing on Days 0, 7, and 14 of postnatal life only. Parameters of cell-mediated and humoral immune function were investgiated. TCDD suppressed delayed hypersensitivity responses and responses to the mitogens Con A and PHA without affecting humoral immune function. Suppression of T-cell function was selective in that helper function was not suppressed. Transfer of primed T-lymphocytes from TCDD treated and non-treated animals into neonatally thymectomized animals confirmed this. Results indicate that delayed hypersensitivity function and helper function reside in distinct T-cell subsets.

INVESTIGATIONS ON THE EFFECTS OF 2,3,7,8‐TETRACHLORODIBENZO‐p‐DIOXIN (TCDD) ON PARAMETERS OF VARIOUS IMMUNE FUNCTIONS

The effects of TCDD exposure on parameters of immune function during the developmental period were investigated. Exposures were performed in Fischer/Wistar rats. Fetal and neonatal rats were exposed to TCDD through maternal dosing (5 micrograms/Kg) on day 18 of gestation and on days 0, 7, and 14 of postnatal life (group 1). Another group of neonatal rats were exposed to TCDD through maternal dosing on days 0, 7, and 14 of postnatal life only (group 2). Body weights and relative thymus weights were found to be suppressed up to 135 days of age in group 1 but only up to 35 days of age in group 2. Parameters of cell-mediated and humoral immune function were investigated. TCDD suppressed cell-mediated immune function without affecting humoral immune function. TCDD-exposed animals had recovered normal cell-mediated immune function by 270 days of age. A group of inbred Fischer rats was exposed to TCDD as described for group 1 above. At 45 days of age these animals were utilized in lymphocyte homing studies. It was found that TCDD exposure alters homing patterns of lymphocytes from exposed animals when adoptively transferred to untreated animals. In addition, lymphocytes from nonexposed animals did not home normally when injected into TCDD-exposed recipients.

Alterations of the antibody response followingIn Utero exposure to diethylstilbestrol

SummaryThe antibody response to SRBC andE. coli 0127 lipopolysaccharide were determined in offspring from mice exposedin utero to diethylstilbestrol. The antibody response to SRBC, a Tcell dependent antigen, was similar in control and exposed animals. In contrast, the LPS antibody response was suppressed in treated females and enhanced in treated males. These studies indicated thatin utero exposure to DES alters the humoral immune system to T-independent antigens.

Effects of 2,3,7,8-Tetrachlorodibenzofuran (TCDF) on the Immune System in Guinea Pigs

The effects of TCDF exposure on the immune system were investigated in Hartley guinea pigs. TCDF was administered by gavage at doses of 0.05, 0.17, 0.5 or 1.0 microgram/kg body weight once weekly for six weeks. Thymus/body weight ratios were suppressed in the higher dosage groups. Parameters of cell-mediated and humoral immune function were investigated. TCDF modestly suppressed cell-mediated immune function and had slight effects on humoral-mediated functions. TCDF immunosuppression appears similar to that induced following exposure to TCDD.

ASSESSMENT OF IMMUNOLOGIC ALTERATIONS CAUSED BY HALOGENATED AROMATIC HYDROCARBONS

The rational for employing a particular approach and some of the difficulties that can be encountered when adapting immune surveillance to toxicology studies in experimental animals are discussed. Detailed description of methodology will not be reviewed. In general, assays are selected for their reliability, i.e. fairly standard within a normal population; that are capable of detecting subtle differences in immune status; and are specific for particular aspects of the immune system. Since normal immune responses are directly dependent upon at least three distinct subpopulations of lymphocytes, macrophages and their cooperative interactions as well as a number of indirect factors, it is essential to study multiple parameters to properly evaluate the effects of environmental chemicals on the immune system. Immunologic assessment is further complicated by the fact that the immune effects will vary dependent upon the chemical and dosage level as well as the species and age of the experimental animals.