T Cell-Dependent Antibody Response Tests

Kim CJ, Berlin JA, Bugelski PJ, Haley P, Herzyk DJ. Combined analyses of heterogeneous immunotoxicology studies using functional T cell-dependent antibody response tests. Perspect Exp Clin Immunotoxicol 2007 1 60-73. 

Joseph R. Piccotti, PhD, Fellow, Immunotoxicology, Drug Safety and Metabolism, Schering-Plough Research Institute, 556 Morris Avenue, Summit, NJ 07901, Email joseph.piccotti spcorp.com Chaper 3.1.1 T-Cell Dependent Antibody Response Tests... 

The current practice of using a T-cell-dependent antibody response or natural killer cell function is based on analyses suggesting that these parameters would suffice to identify the vast majority of immunotoxicants.12 However, it is clear that there are exceptions12 and that some immunotoxicants are not effectively identified by these functional tests or by histopathology.3 Thus, it remains possible, particularly if the cost of microarray analysis decreases, that microarrays will eventually prove to be the most practical method available to identify immunotoxicants. 

TDAR = T cell dependent antibody response, DTH (=delayed-type hypersensitivity test) is problematic in NHP. 

Whereas the experimental design is quite standardized regarding maternal aspects, the duration of postnatal infant assessments is rather variable between studies, for example, from 7 days to 720 days in our experience. Evidently there is a need for standardization of the timing and type of test batteries for infants and of the time period the infant should be raised. For behavioral tests, a postnatal observation period of 9 months appears essential since these tests can only by applied from the age of 6 months onward. For evaluation of immune system development, a period of 6 months appears mandatory since from that age onward blood volume is sufficient to conduct several tests, such as the T cell dependent antibody response (TDAR), NK cell... 

Evaluation of Phagocyte Activity. As mentioned above, the ICH S8 guidance on immunotoxicity testing calls for follow-up testing as necessary. If it is determined that follow-up testing is required and the cell types affected in the initial evaluation of a test article are not involved in the more general assay for immune function (the T-Dependent Antibody Response Assay), specihc assays may be conducted to assess the function of a particular cell type such as... 

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