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J Saloga

Publications and source records attributed to J Saloga.

47 records · Page 3Linked to original sources
PubMed1994

Inhibition of the development of immediate hypersensitivity by staphylococcal enterotoxin B.

We investigated the ability of staphylococcal enterotoxin B (SEB) to modify the immediate hypersensitivity response induced in BALB/c mice following sensitization to ovalbumin (OVA), a response mediated by OVA-reactive V beta 8 T cells. Mice were sensitized by skin painting with OVA every second day over a period of 2 weeks. SEB, a potent activator of V beta 8+ T cells, was administered at the same site where OVA was applied (skin of the lower abdomen) following two different protocols. In protocol (A) SEB was injected intradermally 1 day before painting with OVA and on day 7; in protocol B, SEB was injected each time OVA was applied to the skin (eight times). SEB (but not SEA) altered the development of immediate hypersensitivity to OVA, as demonstrated by the reduction in allergen-specific IgE, decreased OVA-specific immediate skin test responsiveness, and prevented the development of increased airways responsiveness after bronchial challenge with OVA. Injections of SEB did not alter the proliferative responses of local draining lymph node cells or spleen mononuclear cells to OVA, indicating that administration of SEB did not inhibit the sensitization of OVA, but shifted the immune response away from an immediate type response (IgE/IgG1) to IgG2a, IgG2b and IgG3. Although both protocols of SEB treatment did not lead to a major deletion of the V beta 8 T cell population, they did reduce the proliferative response of V beta 8+ T cells to OVA. These data indicate that the bacterial toxin SEB is capable of modifying the immediate hypersensitivity response induced by OVA by altering the functional capacity of antigen-reactive V beta 8 T cells.

Allergens↗
PubMed1994

Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants.

To investigate the interleukin-8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensitizer (2,4-dinitrofluorobenzene, 3-n-pentadecylcatechol); (ii) tolerogen (5-methyl-3-n-pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin-8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin-8. Interleukin-8 gene expression was markedly increased upon in vitro stimulation after 1-6 h with contact sensitizers, tolerogen and the irritant. In contrast, interleukin-8 production was not detectable in unstimulated normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin-8 is a response to nonspecific stimuli and may play a critical role in the early response to immunogenic or inflammatory signals in man.

Catechols↗
PubMed1994

Increased airways responsiveness in mice depends on local challenge with antigen.

In Balb/C mice, painting the skin with ovalbumin (OVA) over a period of 14 days resulted in sensitization of the animals. This was documented by the appearance of OVA-specific IgE and IgG1 antibodies and increased total serum IgE levels. In addition, in regional (inguinal) lymph nodes of sensitized animals, OVA-specific T cell proliferative responses and increased IgE and IgG production could be detected in vitro. Sensitized animals also developed immediate cutaneous responses to intradermal injection of OVA. In contrast to previous results following OVA sensitization via the airways, increased airways responsiveness to electrical field stimulation (AREFS) of tracheal smooth muscle preparations was not observed in skin-sensitized mice. Only 24 h after a single local challenge of the airways with aerosolized OVA on Day 14 could a significant increase in AREFS be observed in skin-sensitized but not nonsensitized control mice. These data indicate that sensitization of Balb/C mice to OVA via the skin provides an effective means for inducing a systemic IgE and IgG1 antibody response and immediate cutaneous hypersensitivity. Despite these IgE and IgG1-mediated responses, however, the development of altered function as reflected in an increase in AREFS was dependent on challenge with the allergen via the airways.

Administration, Cutaneous↗
PubMed1994

Identification and induction of human keratinocyte-derived IL-12.

Interleukin 12 is a heterodimeric molecule that serves as a potent co-stimulator enhancing the development of Th1 cells. As one of the classical Th1 cell-mediated responses is contact sensitivity in skin, we wondered whether IL-12 might be produced by epidermal cells and serve as a mediator of this immune response. Using a sensitive, quantitative PCR technique we demonstrate that p35 chain mRNA of IL-12 is produced constitutively by human epidermal cells, whereas p40 chain mRNA can only be detected in epidermis treated with contact allergen, but not epidermis exposed to irritants or tolerogens. Time course studies showed a dramatic induction of IL-12 p40 mRNA 4 h after in vivo allergen treatment reaching peak strength after 6 h. In cell depletion assays we show that epidermal keratinocytes are the major source of this cytokine in the epidermis. This was further supported by analysis of mRNA derived from the human keratinocyte cell line HaCat expressing IL-12 p35 and p40 mRNA upon stimulation. The presence of bioactive IL-12 in supernatants derived from allergen-stimulated epidermal cells was demonstrated by IL-12-specific bioassay. Additional evidence for the functional importance of IL-12 in primary immune reactions in skin was obtained in allogeneic proliferation assays using human haptenated epidermal cells containing Langerhans cells as APC and allogeneic CD4+ T cells as responders. Anti-IL-12 mAb inhibited the proliferation of T cells by approximately 50%. In aggregate our data demonstrate that nonlymphoid keratinocytes are capable of producing functional IL-12 and provide evidence for the functional significance of IL-12 in primary immune responses in skin.

Antibodies, Monoclonal↗
PubMed1993

Specific V beta T cell subsets mediate the immediate hypersensitivity response to ragweed allergen.

T and B cell responses after sensitization to ragweed (RW) were examined in a mouse model in which BALB/c mice were exposed to the allergen by ultrasonic nebulization. Sensitization resulted in the stimulation of an IgE anti-RW response and was paralleled by a rise in IgG1 anti-RW titers. Skin testing for immediate cutaneous hypersensitivity revealed the presence of allergic type I reactions to RW. Sensitization to RW in this way was also associated with the development of increased airways responsiveness as determined by electrical field stimulation of preparations of tracheal smooth muscle. Histologic examination of the airways and the lung indicated the presence of a mononuclear cell infiltrate in the mucosa and submucosa of the airways that was accompanied by an enlargement of local draining lymph nodes of the airways and the lung. T cell populations were analyzed for the frequency of V beta-expressing T cells. Such analysis indicated that RW sensitization stimulated the expression of V beta 8.1+, V beta 8.2+, and V beta 13+ T cells in the local lymphoid tissue and of V beta 8.1+, V beta 8.2+, V beta 8.3+, V beta 9+ and V beta 14+ T cells in the spleen. Co-culture of these T cell populations with RW-primed B cells indicated that in the presence of RW, V beta 8.2 T cells stimulated IgE and IgG1 production, whereas the other T cell populations showed a different stimulation profile for Ig isotypes and IgG subclasses. The transfer of V beta 8.2 T cells from sensitized but not from nonsensitized control mice stimulated an allergen-specific IgE and IgG1 response and increased airways responsiveness in naive recipients. These data provide additional support for the pivotal role of specific V beta-expressing T cell subpopulations in the stimulation of IgE/IgG1 production and increased airways responsiveness.

Aerosols↗
PubMed1993

T cells expressing specific V beta elements regulate immunoglobulin E production and airways responsiveness in vivo.

The role of T cells expressing specific V beta elements was examined in the regulation of allergen-specific immunoglobulin (Ig)E production and airways responsiveness (AR). In BALB/c mice, inhalation of the allergen ovalbumin (OVA) induced an IgE anti-OVA response, immediate cutaneous reactivity, and increased AR. These results were associated with an expansion of V beta 8.1/8.2 T cells in local draining lymph nodes of the airways and the lung. Transfer of V beta 8.1/8.2 T cells from sensitized mice stimulated an IgE anti-OVA response, immediate cutaneous hypersensitivity, and increased AR in naive syngeneic recipients. In contrast, OVA-reactive V beta 2 T cells inhibited these effects. These data demonstrate for the first time that T cells with different V beta specificities play a critical role in the in vivo regulation of allergen-specific IgE production and AR.

Allergens↗
PubMed1993

Characterization of the progression signal for human T-cell proliferation provided by monoclonal antibodies to the CD3-TCR complex.

Following T-cell activation, two distinct stages in the proliferative response can be identified. The first stage or state of competence (G0 to G1 transition) is defined by the acquisition of the ability of activated T cells to proliferate in response to growth factors. The second or progression phase relates to the progression of cells to DNA synthesis in response to exogenous growth factors (e.g., IL-2) or inducers of growth factor synthesis (e.g., phorbol esters). In the present manuscript we provide evidence that soluble monoclonal antibodies (mAbs) to CD3 or the T-cell receptor (TCR), similar to the phorbol esters, can induce IL-2 production and cell proliferation in competent but not resting T cells. The data indicate the role of CD3-TCR complex triggering not only as an "activating or competence signal" but demonstrate its capacity to signal in the progression phase as well. However, there were distinct differences when competent T cells were stimulated by phorbol ester compared to soluble antibodies to CD3 or TCR. Antibodies to the CD3-TCR complex, when compared to phorbol ester, induced less proliferation in competent, memory T cells (CD45RO) than in competent, naive T cells (CD45RA). In contrast to phorbol ester, the induction of IL-2 transcription and cell proliferation in competent cells by soluble mAbs BMA 031 (anti-alpha/beta T-cell receptor) or OKT3 (anti-CD3) was inhibited by cyclosporin A (CsA). This implies that in activated T cells there is a step between activation of the CD3-TCR complex and the point(s) of action of phorbol ester that is susceptible to CsA in activated cells. Alternatively, the data may indicate involvement of different regulatory elements with different sensitivities to CsA for the induction of IL-2 transcription by phorbol ester or antibodies to the CD3-TCR complex.

Antibodies, Monoclonal↗
PubMed1993

Development and transfer of immediate cutaneous hypersensitivity in mice exposed to aerosolized antigen.

We previously showed that BALB/c mice sensitized to ovalbumin (OVA) by brief daily inhalations of antigen over 10 consecutive days exhibit elevated antigen-specific serum IgE antibody levels and increased airways responsiveness. For the first time, we now show that animals sensitized in this fashion to either OVA or ragweed (RGW) develop immediate hypersensitivity skin test reactions when challenged 2 d after completion of the sensitization protocol. Skin testing, performed by direct assessment of wheal formation after intradermal injection of allergen, was sensitive and specific, since animals exposed to RGW by inhalation only responded to RGW, and OVA-sensitized animals responded only to OVA. Positive reactions were associated with mast cell degranulation, whereas control injections were not. Since only sensitized IgE high responder BALB/c mice but neither nonsensitized BALB/c mice nor OVA-sensitized IgE low responder SJL/J mice exhibited wheal responses, induction of OVA-specific IgE appeared to be essential for the mediation of OVA-specific immediate hypersensitivity reactions of the skin in this model. Passive cutaneous anaphylaxis (PCA) testing confirmed the presence of antigen-specific IgE in the serum. Mice that developed IgG (predominantly IgG2b) anti-OVA antibodies did not respond to OVA injection, indicating that OVA-specific IgG was not involved in this system. Further support for the role of IgE in the immediate hypersensitivity response included the wheal response to intradermal injection of anti-IgE antibody that occurred in OVA- and RGW-sensitized mice at 10-fold lower concentrations than in nonsensitized BALB/c mice and not in sensitized SJL/J mice. After transfer of mononuclear cells from peribronchial lymph nodes of OVA- or RGW-sensitized BALB/c mice, naive, syngeneic recipients developed antigen-specific IgE and specific immediate hypersensitivity responses, indicating that the local lymphoid tissue at the site of sensitization can transfer responsiveness to these allergens. These results demonstrate for the first time the ability to elicit and study IgE-mediated immediate skin hypersensitivity responses in the mouse and illustrate the association of increased antigen-specific and total serum IgE levels, airways hyperresponsiveness, and antigen-specific immediate cutaneous reactivity after sensitization to allergen via the airways.

Aerosols↗
PubMed1988

Ultrastructural cytochemical visualization of chromium in the skin of sensitized guinea pigs.

Using a modified sulfide silver method for electron microscopy, the intraepidermal and intracellular localization of epicutaneously applied potassium dichromate was investigated at varying times in sensitized and nonsensitized guinea pigs. The hapten penetrated rapidly into the epidermis. There was a homogeneous extra- and intracellular staining of the keratinocytes in the upper epidermis. The basal and suprabasal cells, by contrast, exhibited a predominant extracellular and plasma membrane localization of the silver grains. This membrane staining pattern was also observed in the Langerhans cells showing cellular and endocytotic activation in the sensitized animals. No specific cellular uptake of the hapten by the Langerhans cells was found. These results demonstrate that the epicutaneous application of chromate resulted in a characteristic intraepidermal distribution which may be related to the epidermal conversion of the hexavalent chromate to the immunogenic trivalent form. Moreover, the absent intracellular localization of the hapten in the activated Langerhans cells supports the notion that contact allergens can be presented to T cells without prior intracellular processing.

Animals↗
PubMedDate not supplied

Superantigens in skin diseases.

Superantigens are strong modulators of the immune system affecting T cells, antigen-presenting cells and other MHC class II-positive cells directly and many other cells indirectly, e.g. mast cells that have bound IgE specific for superantigens. The strong immunomodulatory effects, which are outlined in this article besides the biological properties of superantigens, strongly influence immunologically-mediated disorders including inflammatory skin diseases like atopic dermatitis and psoriasis, which are the focus of this article.

Animals↗