Different patterns of lymphokine secretion have been observed with different subsets of T cells: INF gamma and IL-2 are produced by the Th1 subset, while IL-4, IL-5, and IL-10 are produced by the Th2 subset, as originally documented for cloned CD T-cell lines from mice (Mosmann & Coffman, 1989).
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In particular, SCID mice co-implanted with human fetal thymus and liver tissue fragments (SCID/hu mice) offer the possibility of studying the human thymus in vivo in an isolated xenogeneic environment (McCune et al., 1988; Namikawa et al., 1990) and the effects of immunotoxicants on these grafts.
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Studies have been conducted in mice, and to a lesser extent in rats, to investigate the specificity, precision (reproducibility), sensitivity, accuracy, and relevance for the assessment of risk to human health of a variety of measures of immune status.
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PCB treatment was shown to protect mice and rats against Ehrlich's tumour (Keck, 1981) and Walker 256 tumours (Kerkvliet & Kimeldorf, 1977), shown as reduced tumour growth and metastasis after transplantation; in other studies, however, no influence of PCB on tumour-cell implants was reported (Koller, 1977; Loose et al., 1981).
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4.5.2 Transgenic mice The development of molecular genetic techniques has allowed not only the isolation and analysis of specific genes but also the manipulation of embryonic genes.
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The placement of human fetal thymus under the SCID mouse renal capsule, followed by an intravenous injection of fetal liver cells (McCune et al., 1988), and co-implantation of human fetal liver and fetal thymus under the renal capsule of SCID mice (Namikawa et al., 1990) have resulted in reconstitution of SCID/hu mice; the fetal thymic implants increased in size, and were found to be vascularized.
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With this restriction in mind, the outcome of experiments with SCID/hu and SCID/ra mice can be used to compare the sensitivity of the human and rat thymus and can thus yield important information for the process of human risk assessment.