International Archives of Allergy and Immunology
Original Paper
Cytokine Production, Lymphocyte Proliferation and T-Cell Receptor Vβ Expression in Primary Peripheral Blood Mononuclear Cell Cultures from Nickel-Allergic IndividualsCederbrant K.a,c · Anderson C.b · Andersson T.b,† · Marcusson-Ståhl M.c · Hultman P.aaDepartment of Molecular and Clinical Medicine, Division of Molecular and Immunological Pathology (AIR), bDepartment of Biomedicine and Surgery, Division of Dermatology, Linköping University, Linköping, and cAstraZeneca R&D Södertälje, Safety Assessment, Södertälje, Sweden
|
|
Log in to MyKarger to check if you already have access to this content.
KAB
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price.
Article / Publication Details
Received: April 08, 2003
Accepted: August 14, 2003
Published online: January 14, 2004
Issue release date: December 2003
Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 2
ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)
For additional information: https://www.karger.com/IAA
Abstract
Background: Clinical history and patch test constitute the two cornerstones in the diagnosis of nickel (Ni) allergy. Due to technical and interpretative limits of the patch test, the in vitro lymphocyte transformation test (LTT) has been developed for confirming contact allergy; however, most studies show an overlap in lymphocyte proliferation between Ni-allergic and nonallergic subjects using the LTT. The aim of this study was to see if the secretion of cytokines, especially interleukin (IL)-10 and IL-17, or the use of T-cell receptor (TCR) Vβ families in Ni-stimulated primary peripheral blood mononuclear cell (PBMC) cultures might be more useful for discriminating between allergic and nonallergic subjects. Methods: Ni2+-stimulated primary PBMC cultures derived from female subjects diagnosed as Ni-allergic (n = 5) or nonallergic (n = 5) on the basis of a positive or negative patch test were assessed for cell proliferation by tritiated thymidine incorporation and for production of interferon-γ, IL-4, IL-10 and IL-17 in the culture supernatant by ELISA. The immunophenotype and TCR-Vβ family affiliation of the Ni2+-induced lymphoblasts were determined by flow cytometry. Results: Lymphocytes from Ni-allergic individuals challenged with a high and a low concentration of Ni showed significantly higher cell proliferation than lymphocytes from nonallergic individuals, but all subjects showed a positive LTT result (stimulation index >2). We found a significantly higher release of IL-10 in Ni2+-treated cultures from Ni-allergic compared with nonallergic subjects that provided better separation between individuals in the two groups than did lymphocyte proliferation. The proliferating lymphoblasts were predominantly CD4+, and in 2 of the 5 Ni-allergic subjects, but in none of the 5 nonallergic subjects, the CD4+ lymphoblasts showed a dominance of TCR-Vβ17. Conclusions: Determination of IL-10 production in primary PBMC cultures is a potentially promising in vitro method for discrimination of Ni allergy in females, as compared with cell proliferation.
© 2003 S. Karger AG, Basel
Related Articles:
References
- Kligman A: The identification of contact allergens by human assay. 3. The maximization test: A procedure for screening and rating contact sensitizers. J Invest Dermatol 1966;47:393–409.
-
Hostynek JJ: Aspects of Nickel Allergy: Epidemiology, etiology, immune reactions, prevention, and therapy; in Hostynek JJ , Maibach HI (eds): Nickel and the Skin: Absorption, Immunology, Epidemiology, and Metallurgy. Boca Raton, CRC Press, 2002, pp 2–38.
-
Menné T, Holm N: Nickel allergy in a female twin population. Int J Dermatol 1983;22:22–28.
External Resources
-
Hostynek JJ, Reagan KE, Maibach HI: Diagnostic testing for nickel allergic hypersensitivity: Patch testing versus lymphocyte transformation test; in Hostynek JJ, Maibach HI (eds): Nickel and the Skin: Absorption, Immunology, Epidemiology, and Metallurgy. Boca Raton, CRC Press, 2002, pp 167–184.
-
Agrup G: Sensitization induced by patch testing. Br J Dermatol 1968;80:632–634.
- Meneghini B, Angelini G: Behaviour of contact allergy and new sensitivities on subsequent patch tests. Contact Dermatitis 1977;3:138–142.
- Silvennoinen-Kassinen S: The specificity of nickel sulphate reaction in vitro: A familial study and a study of chromium-allergic subjects. Scand J Immunol 1981;13:231–235.
-
Nordlind K: Fractionation of human thymocytes and peripheral blood lymphocytes on Percoll density gradients and DNA synthesis stimulating effect of mercuric chloride. Int Arch Allergy Appl Immunol 1984;75:16–19.
External Resources
- Cavani A, Mei D, Guerra E, Corinti S, Giani M, Pirrotta L, Puddu P, Girolomoni G: Patients with allergic contact dermatitis to nickel and nonallergic individuals display different nickel-specific T-cell responses. Evidence for the presence of effector CD8+ and regulatory CD4+ T cells. J Invest Dermatol 1998;111:621–628.
- Moulon C, Wild D, Dormoy A, Weltzien H: MHC-dependent and -independent activation of human nickel-specific CD8+ cytotoxic T cells from allergic donors. J Invest Dermatol 1998;111:360–366.
- Wang B, Fujisawa H, Zhuang L, Freed I, Howell B, Shahid S, Shivji G, Mak T, Sauder D: CD4+ Th1 and CD8+ type 1 cytotoxic T cells both play a crucial role in the full development of contact hypersensitivity. J Immunol 2000;165:6783–6790.
- Cavani A, Nasorri F, Prezzi C, Sebastinai S, Girolomoni G: Human CD4+ T lymphocytes with remarkable regulatory functions on dendritic cells and nickel-specific Th1 immune responses. J Invest Dermatol 2000;114:295–302.
- Sinigaglia F, Scheidegger D, Garotta G, Scherper R, Pletscher M, Lanzavecchia A: Isolation and characterization of Ni-specific clones from patients with Ni-contact dermatitis. J Immunol 1985;135:3929–3932.
- Kapsenberg M, Wierenga E, Stiekema F, Tiggelman A, Bos J: Th 1 lymphokine production profiles of nickel-specific CD4+ T-lymphocyte clones from nickel contact allergic and non-allergic individuals. J Invest Dermatol 1992;98:59–63.
-
Silvennoinen-Kassinen S, Poikonen K, Ikäheimo I: Characterization of nickel-specific T-cell clones. Scand J Immunol 1991;33:429–434.
External Resources
- Probst P, Küntzlin D, Fletscher B: Th2-type infiltrating T cells in nickel-induced contact dermatitis. Cell Immunol 1995;165:134–140.
- Werfel T, Hentschel M, Kapp A, Renz A: Dichotomy of blood- and skin-derived IL-4-producing allergen-specific T cells and restricted Vβ repertoire in nickel-mediated contact dermatitis. J Immunol 1997;158:2500–2505.
-
van der Broeke L, Gräslund A, Larsson P, Nilsson J, Wahlberg J, Scheynius A, Karlberg A: Free radicals as potential mediators of metal allergy: Effect of ascorbic acid on lymphocyte proliferation and IFN-gamma production in contact allergy to Ni2+ and Co2+. Arch Derm Res 1998;292:285–291.
External Resources
- Borg L, Christensen J, Kristiansen J: Nickel-induced cytokine production from mononuclear cells in nickel-sensitive individuals and controls. Cytokine profiles in nickel-sensitive individuals with nickel allergy-related hand eczema before and after nickel challenge. Arch Derm Res 2000;292:285–291.
-
Falsafi-Amin H, Lundeberg L, Bakhiet M, Nordlind K: Early DNA synthesis and cytokine expression in the nickel activation of peripheral blood mononuclear cells in nickel-allergic subjects. Int Arch Allergy Appl Immunol 2000;123:170–176.
-
Jakobson E, Masjedi K, Ahlborg N, Lundeberg L, Karlberg A-T, Scheynius A: Cytokine production in nickel-sensitized individuals analysed with enzyme-linked immunospot assay: Possible implication for diagnosis. Br J Dermatol 2002;147:442–449.
External Resources
-
Szepietowski J, McKenzie R, Keohane S, Aldridge R, Hunter J: Atopic and non-atopic individuals react to nickel challenge in a similar way. A study of the cytokine profile in nickel-induced contact dermatitis. Br J Dermatol 1997;137:195–200.
External Resources
-
Shin H, Benbernou N, Esnault S, Guenounou M: Expression of IL-17 in human memory CD45RO+ T lymphocytes and its regulation by protein kinase A pathway. Cytokine 1998;11:257–266.
External Resources
- Albanesi C, Cavani A, Girolomoni G: IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: Synergistic or antagonistic effects with IFN-γ and TNF-α. J Immunol 1999;162:494–502.
-
Moulon C, Vollmer J, Weltzien H: Characterization of processing requirements and metal cross-reactivities in T-cell clones from patients with allergic contact dermatitis to nickel. Eur J Immunol 1995;25:3308–3315.
External Resources
- Emtestam L, Zetterquist H, Olerup O: HLA-DR, -DQ, -DP alleles in nickel, chromium, and/or cobalt-sensitive individuals: genomic analysis based on restriction fragment length polymorphisms. J Invest Dermatol 1993;100:271–274.
-
Zollner T, Neubert C, Wettstein A, Boencke W, Manfras W, Böhm B, Sterry W: The T cell receptor Vβ repertoire of nickel-specific T cells. Arch Derm Res 1998;290:397–401.
External Resources
-
Büdinger L, Neuser N, Totzke U, Merk H, Hertl M: Preferential usage of TCR-Vβ17 by peripheral and cutaneous T cells in nickel-induced contact dermatitis. J Immunol 2001;167:6038–6044.
External Resources
- Vollmer J, Fritz M, Dormoy A, Weltzien H, Moulon C: Dominance of the BV 17 element in nickel-specific human T-cell receptors relates to severity of contact sensitivity. Eur J Immunol 1997;27:1865–1874.
-
Wahlberg J: Patch testing; in Rycroft J, Menné T, Frosch P (eds): Textbook of Contact Dermatitis. Berlin, Springer, 1995, pp 239–268.
-
Cederbrant K, Marcusson-Ståhl M, Hultman P: Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects. Clin Exp Allergy 2000;30:1450–1459.
External Resources
-
Cederbrant K, Gunnarsson L-G, Hultman P, Norda R, Tibbling-Grahn L: In vitro lymphoproliferative assays with HgCl2 cannot identify patients with systemic symptoms attributed to dental amalgam. J Dent Res 1999;78:1450–1458.
External Resources
- Kappler J, Kotzin B, Herron L, Gelfand E, Bigler R, Boylston A, Carrel S, Posnett D, Choi Y, Marrack P: Vβ-specific stimulation of human T-cells by staphylococcal toxins. Science 1989;244:811–813.
-
Mocellin S, Panelli M, Wang E, Nagorsen D, Marincola F: The dual role of IL-10. Trends Immunol 2003;24:36–43.
External Resources
- Ulfgren A, Klareskog L, Lindberg M: An immunhistochemical analysis of cytokine expression in allergic and irritant contact dermatitis. Acta Derm Venereol (Stockh) 2000;80:167–170.
- Groux H, O’Garra A, Bigler R, Rouleau M, Antonenko S, de Vries J, Roncarolo M-C: A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997;389:737–742.
- Moore K, de Waal Malefy R, Coffman R, O’Garra A: Interleukin-10 and the interleukin-10 receptor. Ann Rev Immunol 2001;19:683–765.
- Groux H, Bigler M, de Vries J, Roncarolo M: Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells. J Immunol 1998;160:3188–3193.
- Levings M, Sangregorio R, Galbiati F, Squadrone S, de Waal Malefyt R, Roncarolo M-C: IFN-α and IL-10 induce the differentiation of human type 1 regulatory cells. J Immunol 2001;166:5530–5539.
- Dunn DA, Gadenne AS, Simha S, Lerner EA, Bigby M, Bleicher PA: T cell receptor Vβ expression in normal human skin. Proc Natl Acad Sci USA 1993;90:1267–1273.
Article / Publication Details
Received: April 08, 2003
Accepted: August 14, 2003
Published online: January 14, 2004
Issue release date: December 2003
Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 2
ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)
For additional information: https://www.karger.com/IAA
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Get Permission