Relationship between cutaneous delayed hypersensitivity and cell-mediated immunity in vitro responses assessed by diphtheria and tetanus toxoids

Galant, Stanley P.; Flod, Natalie E.; Shimizu, Irene; Granger, Gale A.; Groncy, Charles E.

doi:10.1016/0091-6749(77)90139-7

Cited by 25 publications

(5 citation statements)

References 16 publications

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“…This is in agreement with earlier human data, which evidenced a good correlation between in vitro cell-mediated immune responses and DTH 19 ,20,21 . Although DTH models have been developed and used since the early days of immunotoxicology 2 ,3 , limited attention has been paid to these models until recently.…”

Section: Discussionsupporting

confidence: 93%

Development of a Delayed-Type Hypersensitivity (DTH) Model in the Cynomolgus Monkey

et al. 2012

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Although a T-dependent antibody response (TDAR) assay is generally recommended as the first-line immune function assay in nonclinical immunotoxicity evaluation, second-line assays such as delayed-type hypersensitivity (DTH) to measure cell-mediated responses can provide helpful additional information. In this study, male Cynomolgus monkeys were injected intramuscularly either once or twice with 1 mg Keyhole Limpet Hemocyanin (KLH) or twice with a commercially available tetanus vaccine (40 IU tetanus toxoid + 0.06 mg aluminum hydroxide). All animals were subsequently challenged by intradermal injections of the same antigen or aluminum hydroxide after 4, 6 and 8 weeks. Clinical reactions at the injection sites were scored 24, 48 and 72 h post challenge. Skin biopsies were taken on completion of the observation period after each challenge for standard histological examination and immunolabeling using CD3 (T lymphocytes), CD19 (B lymphocytes) and CD68 (macrophages) antibodies. Tetanus toxoid induced stronger clinical reactions than KLH, whereas aluminum hydroxide induced no clinical reaction. Perivascular mononuclear cell infiltrates, a histopathological finding consistent with a DTH reaction, were seen after all challenges with tetanus toxoid or KLH, but not with aluminum hydroxide. Immunohistochemistry evidenced the presence of T lymphocytes and macrophages within these infiltrates. These results suggest that tetanus toxoid adjuvanted with aluminum hydroxide can induce a consistent DTH response for use as a model of cell-mediated response in Cynomolgus monkeys.

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Section: Discussionsupporting

confidence: 93%

Development of a Delayed-Type Hypersensitivity (DTH) Model in the Cynomolgus Monkey

et al. 2012

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“…The pioneering NTP interlaboratory immunotoxicity validation study in B6C3F1 mice, which tested a battery of reference compounds using various endpoints, showed that DTH is a predictor of cell-mediated immunity comparable to the in vitro lymphocyte proliferation assay 18 . This is in agreement with earlier human data, which evidenced a good correlation between in vitro cell-mediated immune responses and DTH [19][20][21] . Although DTH models have been developed and used since the early days of immunotoxicology 2,3 , limited attention has been paid to these models until recently.…”

Section: Discussionsupporting

confidence: 82%

Development of a delayed-type hypersensitivity (DTH) model in the Cynomolgus monkey

Bouchez¹,

Gervais²,

Fleurance³

et al. 2011

Toxicology Letters

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“…Results of the present study did indicate that subclinical PT altered cell-mediated immunity of ewes. The lack of correspondence between results of in vivo and in vitro evaluations of cell-mediated immunity may have been a result of the different sensitivities of the 2 assays 27 or, as suggested by others, may indicate effects on cells in vivo that were not present in the in vitro cultures or variations in the populations of lymphocytes (peripheral blood lymphocytes vs lymphocytes in the lymph). 28 Singh et al 14 reported that ewes with clinical signs of experimentally induced PT had a significant depression in cell-mediated immune responses, as assessed by the lymphocyte migration inhibition test and the 2,4-dinitrochlorobenzene skin hypersensitivity test.…”

Section: Discussionmentioning

confidence: 95%

Effects of subclinical pregnancy toxemia on immune responses in sheep

Lacetera¹,

Bernabucci²,

Ronchi³

et al. 2001

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Relationship between cutaneous delayed hypersensitivity and cell-mediated immunity in vitro responses assessed by diphtheria and tetanus toxoids

Cited by 25 publications

References 16 publications

Development of a Delayed-Type Hypersensitivity (DTH) Model in the Cynomolgus Monkey

Development of a Delayed-Type Hypersensitivity (DTH) Model in the Cynomolgus Monkey

Development of a delayed-type hypersensitivity (DTH) model in the Cynomolgus monkey

Effects of subclinical pregnancy toxemia on immune responses in sheep

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