Measles virus (MV) causes profound immunosuppression, resulting in high infant mortality. The mechanisms are poorly understood, largely due to the lack of a suitable animal model. Here, we report that particular MV proteins, in the absence of MV replication, could generate a systemic immunosuppression in mice through two pathways: (1) via MV-nucleoprotein and its receptor FcgammaR on dendritic cells; and (2) via virus envelope glycoproteins and the MV-hemagglutinin cellular receptor, CD46. The effects comprise reduced hypersensitivity responses associated with impaired function of dendritic cells, decreased production of IL-12, and the loss of antigen-specific T cell proliferation. These results introduce a novel model for testing the immunosuppressive potential of anti-measles vaccines and reveal a specific mechanism of MV-induced modulation of inflammatory reactions.

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Allergic contact dermatitis (ACD) is mediated by hapten-specific CD8+ T cells and downregulated by CD4+ T cells. We have recently shown in a model of ACD to weak haptens that priming of IFNgamma-producing CD8+ T cells and the development of skin inflammation could be obtained in mice deficient in CD4+ T cells. Here we show that IFNgamma production by lymph node (LN) cells draining the site of skin sensitization of CD4+ T-cell-deficient mice is a marker of the sensitizing properties of weak haptens. LN cells from mice sensitized as in the classical local lymph node assay (LLNA) were recovered at day 5, then cultured for 20 hours in the presence of submitogenic doses of phytohemagglutinin, and finally tested for the production of IFNgamma. Results show that: (i) production of INFgamma by LN cells was induced by weak and moderate allergens in a dose-dependent fashion; (ii) the magnitude of IFNgamma production paralleled the sensitizing properties of allergens allowing to classify them as moderate or weak haptens; (iii) chemicals without sensitizing properties were unable to stimulate IFNgamma production by LN cells. Therefore, the IFNgamma LLNA appears as a sensitive, specific, and robust assay to detect weak contact allergens.

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Neutrophil functions were studied in 38 lead-exposed workers compared to 34 controls. Both groups were matched according to age, sex, drinking and smoking habits, ethnic origin and drug intake. Blood lead levels were found to be seven times higher in exposed workers than in controls. Phagocytosis assayed by chemiluminescence was found to be slightly but not significantly altered in exposed workers. In contrast, chemotaxis using the agarose technique was significantly depressed. These results are in agreement with previous in-vitro findings. A further assessment of clinical consequences is warranted.

The popliteal lymph node (PLN) assay has long been proposed as a tool to detect immunotoxicants with the potential to induce systemic autoimmunity. A major problem hampering the further validation of this assay is the need to rule out irritants that cause false-positive PLN responses. The anti-depressant, imipramine, has not been reported to induce systemic autoimmune reactions in treated patients, but has been repeatedly found positive in the PLN assay, suggesting that this is a false-positive response. To test this hypothesis, the effects of imipramine were compared to those of 50% ethanol in C57Bl/6 mice. Footpad edema was evidenced in the few days after injection of both ethanol and imipramine. T-cell depletion using monoclonal antibodies against either CD4+ or CD8+T-lymphocytes prior to the PLN assay did not influence the responses to either ethanol or imipramine. Cytokine (TNF, IL-1, IL-1, IL-2R, IL-6, IL-12 and IFN-) fingerprinting of the PLNs after injection of ethanol and imipramine evidenced the same pattern of responses. These results indicate a closely similar pattern of responses following the footpad injection of either imipramine or ethanol. The conclusion can be drawn that imipramine induces positive responses in the PLN assay via primary (nonspecific) irritation.

We have previously reported that contact sensitivity (CS) to dinitrofluorobenzene (DNFB) in C57BL/6 mice was mediated by MHC class I-restricted CD8+ T cells and down-regulated by MHC class II-restricted CD4+ T cells. In this study, we analyzed the contribution of dendritic cells (DC) in the induction of these two T cell subsets endowed with opposite functions. Hapten-pulsed skin- and bone marrow-derived DC, obtained from either normal C57BL/6 mice or from MHC class II (I+II−) and MHC class I (I−II+)-deficient mice, were tested for their ability to prime normal mice for CS to dinitrofluorobenzene. Expression of MHC class I molecules by transferred DC was mandatory both for the induction of CS and for the generation of hapten-specific CD8+ T cells in lymphoid organs. I+II− DC were as potent as I+II+ DC in priming for CS, demonstrating that activation of effector CD8+ T cells can occur independently of CD4+ T cell help. I−II+ DC could not immunize for CS, although they could sensitize for a delayed-type hypersensitivity reaction to protein Ags. Moreover, I−II+ DC injected simultaneously with cutaneous sensitization down-regulated the inflammatory response, suggesting that hapten presentation by MHC class II molecules could prime regulatory CD4+ T cells. These results indicate that DC can present haptenated peptides by both MHC class I and class II molecules and activate Ag-specific CD8+ effector and CD4+ regulatory T cell subsets, concurrently and independently.