Contact sensitivity (CS) is a form of delayed‐type hypersensitivity to haptens applied epicutaneously and is thought to be mediated, like classical delayed‐type hypersensitivity responses, by CD4+ T helper‐1 cells. The aim of this study was to identify the effector T cells involved in CS. We studied CS to the strongly sensitizing hapten dinitrofluorobenzene (DNFB) in mice rendered deficient by homologous recombination in either major histocompatibility complex (MHC) class I, MHC class II, or both, and which exhibited deficiencies in, respectively, CD8+, CD4+, or both, T cells. MHC class I single‐deficient and MHC class I/class II double‐deficient mice, both of which have a drastic reduction in the number of CD8+ T cells, were unable to mount a CS response to DNFB. In contrast, both MHC class II‐deficient mice and normal mice treated with an anti‐CD4 monoclonal antibody (mAb) developed exaggerated and persistent responses relative to heterozygous control littermates. Furthermore, anti‐CD8 mAb depletion of class II‐deficient mice totally abolished their ability to mount an inflammatory response to DNFB. Removal of residual CD4+ T cells in class II‐deficient mice by anti‐CD4 mAb treatment did not diminish the intensity of CS. These data clearly demonstrate that class I‐restricted CD8+ T cells are sufficient for the induction of CS to DNFB, and further support the idea that MHC class II‐restricted CD4+ T cells down‐regulate this inflammatory response.

Contact sensitivity to para-phenylenediamine (PPD) is a frequent delayed-type hypersensitivity resulting in contact dermatitis. The aim of the present study, conducted in 16 patients allergic to PPD (as assessed by a positive patch test), was to get better insight into the mechanism of T-cell activation in PPD contact sensitivity. PPD was unable to induce significant proliferation of T cells from a first set of 9 patients. In 7 further patients, lymphocyte proliferation was assessed using PPD and 2 PPD metabolites, namely Bandrowski’s base (BB) and benzoquinone (BQ). BB specifically stimulated T-cell proliferation in a dose-dependent fashion in all 7 patients whereas BQ, like PPD, was ineffective. The peripheral blood mononuclear cells (PBMC) of 8 PPD nonallergic individuals did not respond to either PPD, BB or BQ. We concluded from this study that: (1) the immunogenic hapten in PPD hypersensitivity is not PPD itself, and (2) BB might be the oxidative derivative of PPD endowed with T-cell-activating properties. Further support to this statement was provided by the observation that a T cell line derived from PBMC of a PPD-allergic patient in the presence of PPD responded to BB but not to PPD. Our in vitro results suggest that PPD is a prohapten which when applied on the skin is metabolized and converted into products (such as BB) which are the immunogenic haptens able to activate specific T cells.

Murine models for the assessment of the contact sensitizing properties of chemicals rely on mouse ear swelling tests (Mest), which are not sensitive enough to detect weak sensitizers. The aim of the present study was to develop in mice an adjuvant-free Mest appropriate for in vivo detection of any type of sensitizer (weak to strong), and useful for in vitro assessment of contact sensitivity (CS). 3 haptens were tested: dinitrochlorobenzene (DNCB), para-phenylenediamine (pPD) and isoeugenol. We compared various protocols for induction of the CS reaction, differing by the site of induction, the number of applications and the concentrations of the 3 haptens. Comparison of the induction site for optimal CS reaction showed that, in Balb/c mice, the back was a better site of induction than the abdomen. Detection of the sensitizing properties of weak sensitizers (pPD, isoeugenol) was possible using an adjuvant-free protocol, provided that the induction phase comprised hapten applications on 3 consecutive days on the backs of animals. For DNCB, one application was sufficient to obtain optimal CS reaction. For all 3 haptens, a secondary response in vitro was obtained using semi-purified lymph node T cells from animals sensitized 5 days before with the optimized Mest. These results demonstrate that the Mest could be a useful experimental model for the study of all types of contact sensitizers.

The objective of this study was to assess the effects of fishmeal (FM) replacement with 0, 350 or 700 g/kg soybean meal (SBM) in combination with the supplementation of lactic acid (LA; 0, 10 or 20 g/kg) in the diets of juvenile beluga sturgeon (Huso huso; 700 ± 30 g). Nine isonitrogenous (400 g/kg protein) and isoenergetic (18 MJ/kg) diets were fed to beluga ad libitum, three times a day, for 60 days. The results showed that replacing FM with SBM without LA significantly reduced fish growth; on the other hand, LA supplementation had positive effects on fish fed diets that FM was replaced by SBM (p < .05). Increasing SBM in the diet altered the fatty acid profiles of the fish, reducing long‐chain polyunsaturated fatty acids and the n‐3/n‐6 fatty acids. High amounts of SBM (700 g/kg) caused reductions in the haematocrit, glucose and cholesterol levels in the blood (p < .05). In addition, the digestibility of protein, fat, dry matter and phosphorus was reduced when replacing FM with SBM, however, adding LA to the diets increased fish performance (p < .05), and this improvement was sharper in 2% LA groups. The number of LA bacteria increased significantly with the dietary supplementation of LA (p < .05). Based on these results, replacing 350 g/kg of FM with SBM and adding 20 g/kg LA to their feed do not negatively affect the biological and physiological indices of beluga.

Oral tolerance is defined by immune unresponsiveness after oral administration of soluble antigens and by antigen-specific inhibition of peripheral immune responses induced by prior antigen feeding. The aim of this study was to investigate the implication of the major histocompatibility complex (MHC) class II presentation pathway to CD4+ T cells in oral tolerance of contact sensitivity (CS) to the hapten dinitrofluorobenzene (DNFB). We used MHC class II knockout (AB0/0) and invariant chain knockout (Ii0/0) mice, which have, respectively, a total or partial defect in class II-restricted activation of CD4+ T cells, as well as normal C57BL/6 mice depleted of CD4+ T cells by injection of a specific antibody. Intragastric administration of DNFB prior to skin sensitization induced specific inhibition of contact sensitivity to DNFB in A beta +/0 and Ii+/0 heterozygotes comparable to that observed in C57BL/6 mice. In contrast, no oral tolerance was observed in either MHC class II-deficient A beta 0/0 and Ii0/0 homozygote mutants or in syngeneic anti-CD4-depleted C57Bl/6 mice. Moreover, a single oral administration of DNFB, without skin sensitization, could prime A beta 0/0, Ii0/0 as well as anti-CD4-depleted C57BL/6 mice for DNFB-specific CS. These findings demonstrate that the class II/CD4 pathway is involved in oral tolerance manifested both as the inhibition of CS by hapten feeding prior to skin sensitization, and as immune unresponsiveness of normal mice to oral administration of hapten. Furthermore, our data provide evidence that a single oral feeding with DNFB is able to prime mice for hapten-specific CS, provided that the class II/ CD4 pathway is bypassed.

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