Characterization of an Approach to Developmental Immunotoxicology Assessment in the Rat Using SRBC as the Antigen

Ladics, Gregory S.; Smith, Clyde F.; Bunn, Terry L.; Dietert, Rodney R.; Anderson, Phyllis K.; Wiescinski, Connie M.; Holsapple, Michael P.

doi:10.1080/105172300750048755

Cited by 37 publications

(28 citation statements)

References 43 publications

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“…With both assays, however, variability in the antibody response has been reported to occur when outbred rodents are utilized. Data suggest that the SRBC-speciic ELISA may be incorporated into standard toxicology studies (Ladics et al, 1995;1998), but its use for DIT may be limited (Ladics et al, 2000). In contrast, the AFC assay has been reported to be useful for DIT studies involving post-weaning animals (Ladics et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Increasing attention, however, has been focused on the effects of xenobiotics on the developing immune system (Holladay and Smialowicz, 2000;Dietert et al, 2002;Holsapple et al, 2005). Data on whether the SRBC primary antibody response would be useful in assessing the functionally immature immune system of young animals (e.g., neonates) was discussed (Ladics et al, 2000). Ten-dayold rat pups were unable to generate a primary IgM response to SRBC using either the AFC assay or ELISA due to the apparent immature status of their immune system.…”

Section: Developmental Immunotoxicologymentioning

confidence: 99%

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Primary Immune Response to Sheep Red Blood Cells (SRBC) as the Conventional T-Cell Dependent Antibody Response (TDAR) Test

Ladics

2007

Journal of Immunotoxicology

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The production of antigen-specific antibodies represents a major defense mechanism of humoral immune responses. Several assays have been developed to assess T-cell-dependent antibody responses (TDAR). Of these assays, the antibody forming cell assay (AFC) or plaque forming cell (PFC) assay and ELISA are the two most often used tests to assess immunotoxicity. Historically, the T-cell-dependent antigen of choice has been sheep red blood cells (SRBC). The SRBC AFC assay is considered the "gold standard" for TDAR based on extensive intra-and inter-laboratory validation in mice and has been utilized for over 35 years. The quantification of the primary AFC response (i.e., the specific IgM antibody-forming cell response) was found to provide one of the best predictors of immunotoxicity in mice. The SRBC-specific ELISA is relatively new, with the first publication of the method appearing in 1993. Data from the application of using both the SRBC specific AFC and ELISA for evaluation of potential immunotoxicity of chemicals in rodents and the pros and cons and associated issues of each method were presented. Specifically, the following was discussed: (1) studies investigating the incorporation of the SRBC-specific IgM ELISA in rats on standard toxicology study; (2) characterization of an approach to developmental immunotoxicology assessment in the rat using SRBC as the antigen; and, (3) data from an inter-laboratory study comparing the AFC assay and ELISA in outbred rodents using both cyclophosphamide and dexamethasone.

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Section: Discussionmentioning

confidence: 99%

Section: Developmental Immunotoxicologymentioning

confidence: 99%

Primary Immune Response to Sheep Red Blood Cells (SRBC) as the Conventional T-Cell Dependent Antibody Response (TDAR) Test

Ladics

2007

Journal of Immunotoxicology

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“…Less is known about the development of the immune system in rats (Holsapple, West, and Landreth 2003); however, the general sequence and timing of immune system development in both rats and humans appears to parallel studies in mice where data are available (Landreth 2002). Phenotypic analysis of rats on PND 10 indicated the absence of lymphocytic subsets, and histological analysis of the spleen revealed no germinal centers in either untreated rats or rats immunized with sheep erythrocytes (SRBC; Ladics et al 2000). No anti-SRBC antibodies were detected in rats on PND 10 (ibid.).…”

Section: Relationship Of Immune System Function and Morphologymentioning

confidence: 99%

Histologic Features of Postnatal Development of Immune System Organs in the Sprague-Dawley Rat

Parker¹,

Picut²,

Swanson³

et al. 2015

Toxicol Pathol

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The immune system of the rat undergoes substantial functional and morphological development during the postnatal period. Some aspects of this development are genetically predetermined, while other aspects depend on environmental influences. Detailed information on postnatal development is important in the interpretation of histopathologic findings in juvenile toxicology and pubertal assay studies, as well as other studies conducted in juvenile rats. Studies were conducted to provide detailed characterization of histologic features of the major functional compartments of immune system organs in male and female Sprague-Dawley rats at weekly intervals from the day of birth through postnatal day (PND) 42. Maturation of the individual immune system organs occurred across a range of ages, with histologic maturation of T-cell-related compartments typically occurring prior to maturation of B-cell-related compartments. The sequence of histologic maturation was bone marrow and thymus on PND 14, mesenteric lymph node on PND 21, Peyer's patches and bronchus-associated lymphoid tissue on PND 28, mandibular lymph node, nasopharynx-associated lymphoid tissue, and diffuse mucosal mononuclear cell population of small intestine on PND 35, and spleen on PND 42. An estimation of functional maturation can be made based on the morphological indications of maturity of each compartment of immune system organs, but histologic indications of maturity do not confirm functional immunocompetence.

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“…For example, the TDAR can be performed in the NHP beginning between 2-4 weeks-of-age. However, the primary limitation of the TDAR in rodents relates directly to the post-natal maturation of immunocompetence (e.g., humoral immunity) in that species, and a robust TDAR cannot be measured in young rodents (Kimura et al, 1985;Ladics et al, 2000). Sub-optimal responses can be obtained on post-natal day (PND) 20-30, but responses of sufficient magnitude are only obtained at 40-56 days-of-age, suggesting that for sufficient sensitivity the TDAR should only be performed in adult rodents.…”

Section: Developmental Immunotoxicity Testing Of Pharmaceuticals 217mentioning

confidence: 99%

“…At this time point lymphoid tissues in rats are anatomically intact but relatively inactive. Thus, evaluation of the TDAR is more commonly included at a later timepoint (Kimura et al, 1985;Ladics et al, 2000) such as PND 42-45 when the TDAR is comparable to adult rats. Although SRBC are recommended for use in the TDAR when testing the immunotoxicity of environmental chemicals, keyhole limpet hemocyanin (KLH) is more frequently used when testing the immunotoxicity of pharmaceuticals.…”

Section: T-dependent Antibody Response (Tdar)mentioning

confidence: 99%

Developmental immunotoxicity (DIT) testing of pharmaceuticals: Current practices, state of the science, knowledge gaps, and recommendations

Collinge

Burns‐Naas

Chellman³

et al. 2012

Journal of Immunotoxicology

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Characterization of an Approach to Developmental Immunotoxicology Assessment in the Rat Using SRBC as the Antigen

Cited by 37 publications

References 43 publications

Primary Immune Response to Sheep Red Blood Cells (SRBC) as the Conventional T-Cell Dependent Antibody Response (TDAR) Test

Primary Immune Response to Sheep Red Blood Cells (SRBC) as the Conventional T-Cell Dependent Antibody Response (TDAR) Test

Histologic Features of Postnatal Development of Immune System Organs in the Sprague-Dawley Rat

Developmental immunotoxicity (DIT) testing of pharmaceuticals: Current practices, state of the science, knowledge gaps, and recommendations

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