Publications (5)12.91 Total impact
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Article: Complementary methods for contact hypersensitivity (CHS) evaluation in mice.
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ABSTRACT: Contact hypersensitivity (CHS) is an experimental model of allergic contact dermatitis (ACD) that can be studied in mice. For CHS responses, mice are immunized by painting with a reactive hapten, such as 1-fluoro,- 4,6-dinitrobenzene (DNFB), on the shaved abdominal and chest skin. Subsequently, the ears are challenged with diluted hapten, eliciting 'hypersensitive' ear-swelling reactions, which can be measured with a micrometer. In this manuscript we present complementary methods that can be used to evaluate CHS in mice that include: ear weight, vascular permeability, myeloperoxidase (MPO) activity, IFN-γ concentration in ear extracts and also IFN-γ production by auricular lymph node cells (ELNC). The biochemical evaluation of CHS can be also supported by proliferation assay, measurement of IFN-γ production by skin-draining lymph node cells employing ELISA test and by evaluation of IFN-γ(+) TCRαβ CD8 cells with the use of flow cytometry.Journal of immunological methods 11/2012; · 2.35 Impact Factor -
Article: Epicutaneous immunization with protein antigen induces antigen-non-specific suppression of CD8 T cell mediated contact sensitivity.
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ABSTRACT: Background: Allergic contact dermatitis (ACD) resulting from exposure to low molecular weight chemicals is a common clinical condition in industrialized countries and can be mediated by either Th1 or Tc1 lymphocytes. The animal model of contact sensitivity (CS) is commonly used to study ACD in mice and helps to test new therapeutics. We have previously shown that epicutaneous (EC) immunization with TNP-Ig prior to hapten sensitization inhibits Th1-mediated CS and observed that the suppression is mediated by TCRαβ(+) CD4(+) CD8(+) cells and is TGF-β dependent. More recently we have shown that EC immunization with DNP-BSA induces TCRαβ(+) CD4(+) CD25(+) FoxP3(+) T regulatory (Treg) cells that suppress Tc1-mediated CS. Methods: Animal model of contact sensitivity was used to study skin-induced suppression. Results: Current work employing Tc1-mediated CS shows that skin-induced suppression is dose-dependent and declines with time. Experiments with the four non-cross-reacting antigens 2,4-dinitrophenylated bovine serum albumin (DNP-BSA), ovalbumin (OVA), myelin basic protein (MBP) and immunoglobulins conjugated with oxazolone (OX-Ig) employing models of active suppression, "transfer in" and "transfer out" protocols showed that EC immunization with any tested protein antigen inhibits CS response suggesting lack of antigen-specificity of the investigated phenomenon. Conclusion: The ease of EC generation of antigen-non-specific regulatory cells may have important implications for designing therapeutic schemes aimed at modulating immune responses.Pharmacological reports: PR 11/2012; 64(6):1485-96. · 2.44 Impact Factor -
Article: Epicutaneous immunization with DNP-BSA induces CD4(+) CD25(+) Treg cells that inhibit Tc1-mediated CS.
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ABSTRACT: As we have shown previously that protein antigen applied epicutaneously (EC) in mice inhibits TNP-specific Th1-mediated contact sensitivity (CS), we postulated that the maneuver of EC immunization might also suppress Tc1-dependent CS response. Here we showed that EC immunization of normal mice with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) applied on the skin in the form of a patch induces a state of subsequent unresponsiveness due to regulatory T cells (Treg) that inhibited sensitization and elicitation of effector T-cell responses. Suppression is transferable in vivo by TCRαβ(+) CD4(+) CD25(+) lymphocytes harvested from lymph nodes (LNs) of skin-patched animals. Flow cytometry revealed that EC immunization with DNP-BSA increased TCRαβ(+) CD4(+) CD25(+) FoxP3(+) lymphocytes in subcutaneous LNs, suggesting that observed suppression was mediated by Treg cells. Further, in vitro experiments showed that EC immunization with DNP-BSA prior to 1-fluoro-2,4-dinitrobenzen sensitization suppressed LN cell proliferation and inhibited production of TNF-α, IL-12 and IFN-γ. Using a transwell system or anti-CTLA-4 mAb, we found that EC induced suppression required direct Treg-effector cell contact and is CTLA-4-dependent.Immunology and Cell Biology 01/2012; 90(8):784-95. · 3.66 Impact Factor -
Article: Stimulatory lipids accumulate in the mouse liver within 30 min of contact sensitization to facilitate the activation of Naïve iNKT cells in a CD1d-dependent fashion.
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ABSTRACT: Natural killer T cells with invariant αβ-T cell receptors (TCRs) (iNKT cells) constitute a lipid-responsive arm of the innate immune system that has been implicated in the regulation or promotion of various immune, infectious and neoplastic processes. Contact sensitivity (CS), also known as contact hypersensitivity or allergic contact dermatitis, is one such immune process that begins with topical sensitization to an allergen and culminates in a localized cutaneous inflammatory response after challenge with the same allergen. CS depends on events initiated early in sensitization by hepatic iNKT cells. We have shown previously that these iNKT cells release IL-4 early after skin sensitization to activate B-1 B cells to produce IgM antibodies that aid in local recruitment of the effector T cells. Here, we utilize adoptive transfer techniques in several strains of knockout mice to demonstrate that hepatic lipids isolated 30 min after sensitization are significantly more stimulatory to naïve hepatic iNKT cells than hepatic lipids isolated after sham sensitization. These stimulatory hepatic lipids specifically affect iNKT cells and not B-1 B cells. The downstream CS response is abrogated with anti-CD1d-blocking antibodies, suggesting a critical role of CD1d in the activation of hepatic iNKT cells with these lipids. Hepatocytes may not be essential, as donor hepatic iNKT cells can reconstitute CS without migrating to the recipient mouse liver. Rather, CD1d-expressing liver mononuclear cells are sufficient for activation of iNKT cells. In conclusion, stimulatory lipids accumulate in the liver soon after sensitization and facilitate iNKT cell activation in a CD1d-dependent yet potentially hepatocyte-independent manner.Scandinavian Journal of Immunology 02/2011; 74(1):52-61. · 2.23 Impact Factor -
Article: Participation of iNKT cells in the early and late components of Tc1-mediated DNFB contact sensitivity: cooperative role of γδ-T cells.
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ABSTRACT: Prior studies of classical 24 h responses in TNP-Cl (picryl chloride) allergic contact sensitivity (CS), showed mediation by Th1 cells in CBA mice, and established that 24 h elicitation of responses requires an early 2 h CS-initiating component dependent on iNKT cells, IL-4 and B-1 B cells. Here, we studied the other form of cytotoxic T cell (Tc1) CS in DNFB sensitized BALB/c mice and determined that similar CS-initiation also is required. We systematically tested each step of the initiation pathway in this model. Thus, DNFB Tc1 CS was significantly impaired in iNKT cell deficient CD1d(-/-) and Jα18(-/-) mice, IL4Rα(-/-) and STAT-6(-/-) mice, and also in pan B-cell deficient JH(-/-) mice. Further, the Tc1 DNFB CS-initiating component, like Th1 response to TNP-Cl, was elicited by only 1-day after immunization, due to B-1 cells. In summary, we show that CS-Initiation also is required in Tc1 CS. Further, we have newly determined regulatory support of both the early and late components of DNFB induced Tc1 CS by iNKT cells and γδ-T cells. In summary, both iNKT cells and assisting γδ-T cells are involved in initiating and effector phases of DNFB induced CS.Scandinavian Journal of Immunology 01/2011; 73(5):465-77. · 2.23 Impact Factor
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Institutions
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2012
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Jagiellonian University
- Department of Medical Biotechnology
Kraków, Lesser Poland Voivodeship, Poland -
Yale University
New Haven, CT, USA
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