Risk assessment in immunotoxicology I. Sensitivity and predictability of immune tests

Luster, Michael I.; Portier, Christopher J.; Pait, D. Gayla; White, Kimber L.; Gennings, Chris; Munson, Albert E.; Rosenthal, Gary J.

doi:10.1016/0272-0590(92)90047-l

Cited by 527 publications

(289 citation statements)

References 26 publications

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“…As the traditional models of TDAR assays were developed in the last era, the primary immune response to sheep red blood cells (SRBC) measured by a splenic plaque-forming cell (PFC) or an enzyme-linked immunosorbent assay (ELISA) had been widely used (Luster et al, 1992;Institoris et al, 2002). However, these assay systems with SRBC have inherent drawbacks, including complicated procedures of PFC assay and several variations come primarily from the lots of SRBC employed and the different procedures of SRBC preparation for plate coating among laboratories.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of primary and secondary responses to a T-cell-dependent antigen, keyhole limpet hemocyanin, in rats

Kawai

Ito

Aida

et al. 2012

Journal of Immunotoxicology

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Section: Introductionmentioning

confidence: 99%

Evaluation of primary and secondary responses to a T-cell-dependent antigen, keyhole limpet hemocyanin, in rats

Kawai

Ito

Aida

et al. 2012

Journal of Immunotoxicology

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“…Suppression of antigen-specific antibody responses is considered predictive of immunotoxicity and decreased resistance to infection in rodents (Luster et al, 1992(Luster et al, , 1993Selgrade, 1999); such alterations in murine immune function can be suggestive of health risks in similarly exposed humans (Selgrade, 2007). We previously reported that exposure to !3.75 mg PFOA/kg/day for 15 days suppressed the TDAR in C57BL/6N mice.…”

mentioning

confidence: 99%

Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARαand T- and B-cell targeting

DeWitt

Williams

Creech

et al. 2015

Journal of Immunotoxicology

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T-cell-dependent antibody responses (TDAR) are suppressed in female C57BL/6N mice exposed to !3.75 mg/kg of perfluorooctanoic acid (PFOA) for 15 days. To determine if suppression of humoral immunity by PFOA is peroxisome proliferator activated receptor alpha (PPAR)-dependent and if suppression is associated with specific targeting of T-or B-cells, three separate experiments were conducted: (1) female PPAR constitutive knockout (PPAR KO; B6.129S4-Ppar tm1Gonz N12) and wild-type controls (WT; C57BL/6-Tac) exposed to 0, 7.5, or 30 mg PFOA/kg for 15 days were immunized on Day 11 with a T-cell-dependent antigen and sera then collected for measures of antigen-specific IgM titers (TDAR) 5 days later; (2) female C57BL/6N WT mice exposed to 0, 0.94, 1.88, 3.75, or 7.5 mg PFOA/kg for 15 days were immunized with a T-cellindependent antigen on Day 11 and sera were then collected for analyses of antigen-specific IgM titers (TIAR) 7 days later; and (3) splenic lymphocyte phenotypes were assessed in unimmunized female C57BL/6N WT mice exposed to 0, 3.75, or 7.5 mg PFOA/kg for 10 days to investigate effects of PFOA in the absence of specific immunization. Separate groups of mice were immunized with a T-cell-dependent antigen after 11 days of exposure and splenic lymphocyte sub-populations were assessed after 13 or 15 days of exposure to assess numbers of stimulated cells. The results indicated that exposure to !1.88 mg PFOA/kg suppressed the TIAR; exposure to 30 mg PFOA/kg suppressed the TDAR in both PPAR KO and WT mice. The percentage of splenic B-cells was unchanged. Results obtained in the PPAR KO mice indicated that PPAR suppression of TDAR was independent of PPAR involvement. Suppression of the TIAR and the TDAR with minimal lymphocyte sub-population effects suggested that effects on humoral immunity are likely mediated by disruption of B-cell/plasma cell function.

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“…For example, regulatory agencies (e.g., Environmental Protection Agency and Food and Drug Administration) evaluate environmental chemicals and drugs for potential adverse effects on immunocompetence, typically by using a panel of functional assays (7). Such agents seldom affect a single immunological parameter (8), and there is no effective way at present to predict the impact on host resistance of small to moderate changes in multiple immunological parameters. These considerations are also relevant in estimating the effects of stress, malnutrition, and other environmental influences on resistance to infection or cancer.…”

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confidence: 99%

Quantifying the Relationship Between Multiple Immunological Parameters and Host Resistance: Probing the Limits of Reductionism

Keil¹,

Luebke

Pruett

2001

The Journal of Immunology

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Although reductionist experimental designs are excellent for identifying cells, molecules, or functions involved in resistance to particular microbes or cancer cells, they do not provide an integrated, quantitative view of immune function. In the present study, mice were treated with either dexamethasone (DEX) or cyclosporin A (CyA), and immune function and host resistance were evaluated. Multivariate statistical methods were used to describe the relative importance of a broad range of immunological parameters for host resistance in mice treated with various dosages of DEX. Multiple regression and logistic regression analysis indicated that changes in 24 immunological parameters explained a substantial portion of the changes in resistance to B16F10 tumor cells or streptococcus group B. However, at least 40% of the change in host resistance remained unexplained. DEX at all dosages substantially suppressed numerous relevant immunological parameters, but significantly decreased resistance to Listeria monocytogenes only at the highest dosage. In contrast, CyA substantially decreased resistance to L. monocytogenes at dosages that caused relatively minor suppression of just a few immunological parameters (unfortunately, CyA data and host resistance data for L. monocytogenes were not suitable for multivariate analysis). These results illustrate that mathematical models can be used to explain changes in host resistance on the basis of changes in immune parameters, and that moderate changes in relevant immunological parameters may not produce the types of changes in host resistance expected on the basis of results from reductionist experimental designs.

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Risk assessment in immunotoxicology I. Sensitivity and predictability of immune tests

Cited by 527 publications

References 26 publications

Evaluation of primary and secondary responses to a T-cell-dependent antigen, keyhole limpet hemocyanin, in rats

Evaluation of primary and secondary responses to a T-cell-dependent antigen, keyhole limpet hemocyanin, in rats

Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARαand T- and B-cell targeting

Quantifying the Relationship Between Multiple Immunological Parameters and Host Resistance: Probing the Limits of Reductionism

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