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Expression of ergotope-associated markers of T lymphocytes in atopic dermatitis after in vitro polyclonal activation

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Abstract

The antiergotypic response leads to the formation of effector T cells able to eliminate activated lymphocytes independently of their antigenic specificity, since the targets of these cells are molecules produced during cell activation (ergotopes). In this paper, we describe the level of expression of the ergotope-associated markers CD25, HSP60, and HLA-DR by the T lymphocytes isolated from the blood of atopic dermatitis patients immediately after isolation and after cultivation. After 10-day cultivation in the presence of anti-CD3 antibodies and IL-2, the expression levels of early and late activation markers in T cells have changed: the shares of CD25-positive CD4+ and CD8+ lymphocytes increase to 68 and 47%, respectively, and the share of HLA-DR-positive cells increases to 26 and 33%. The density of HLA-DR molecules on the surface of activated T cells increases more than fivefold. Almost all T cells before and after cultivation express 60 kDa heatshock protein (HSP60); however, the CD4+ cells activated in vitro contain more HSP60 molecules than do the in vitro-activated CD8+ cells and the CD4+ cells of peripheral blood. Thus, the T cells of atopic-dermatitis patients have the status of activated cells because they express sufficient amounts of early and late activation markers; presumably, they can enhance the induction of antiergotypic response when administered to patients. Taking into account that antiergotypic regulation acts on activated T cells independently of their antigenic specificity, immunotherapy utilizing autologous activated T lymphocytes can be of interest as a method for targeted action on pathogenetic components of atopic dermatitis.

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Abbreviations

AD:

atopic dermatitis

MNCs:

mononuclear cells

HLA-DR:

human leukocyte antigen, a major histocompatibility complex class II molecule

HSP:

heat-shock protein

IL-2:

interleukin 2

MHC:

major histocompatibility complex

References

  • Almanzar, G., Öllinger, R., Leuenberger, J., Onestingel, E., Rantner, B., Zehm, S., Cardini, B., van der Zee, R., Grundtman, C., and Wick, G., Autoreactive HSP60 epitope-specific T-cells in early human atherosclerotic lesions, J. Autoimmun., 2012, vol. 39, pp. 441–450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antúnez, C., Torres, M.J., Mayorga, C., Corzo, J.L., Jurado, A., Santamaría-Babi, L.F., Vera, A., and Blanca, M., Cytokine production, activation marker, and skin homing receptor in children with atopic dermatitis and bronchial asthma, Pediatr. Allergy Immunol., 2006, vol. 17, pp. 166–174.

    Article  PubMed  Google Scholar 

  • Chaput, N., Louafi, S., Bardier, A., Charlotte, F., Vaillant, J.C., Ménégaux, F., Rosenzwajg, M., Lemoine, F., Klatzmann, D., and Taieb, J., Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue, Gut, 2009, vol. 58, pp. 520–529.

    Article  CAS  PubMed  Google Scholar 

  • Chen, W., Syldath, U., Bellmann, K., and Kolb, H., Human 60-kDa heat shock protein: a danger signal to the innate immune system, J. Immunol., 1999, vol. 162, pp. 3212–3219.

    CAS  PubMed  Google Scholar 

  • De Graeff-Meeder, E.R., van der Zee, R., Rijkers, G.T., Schuurman, H.J., Kuis, W., Bijlsma, J.W., Zegers, B.J., and van Eden, W., Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juvenile chronic arthritis, Lancet, 1991, vol. 337, pp. 1368–1372.

    Article  PubMed  Google Scholar 

  • De Kleer, I.M., Kamphuis, S.M., Rijkers, G.T., Scholtens, L., Gordon, G., De Jager, W., Häfner, R., van de Zee, R., van Eden, W., Kuis, W., and Prakken, B.J., The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+ T cells directed to human heatshock protein 60 capable of producing the regulatory cytokine interleukin-10, Arthritis Rheum., 2003, vol. 48, pp. 2001–2010.

    Article  PubMed  Google Scholar 

  • Ghio, M., Fabbi, P., Contini, P., Fedele, M., Brunelli, C., Indiveri, F., and Barsotti, A., OxLDL- and HSP-60 antigen-specific CD8(+) T lymphocytes are detectable in the peripheral blood of patients suffering from coronary artery disease, Clin. Exp. Med., 2013, vol. 13, pp. 251–255.

    Article  CAS  PubMed  Google Scholar 

  • Graca, L. and Cobbold, S.P., Identification of regulatory T cells in tolerated allografts, J. Exp. Med., 2002, vol. 195, pp. 1641–1646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herndler-Brandstetter, D., Schwaiger, S., Veel, E., Fehrer, C., Cioca, D.P., Almanzar, G., Keller, M., Pfister, G., Parson, W., Würzner, R., Schönitzer, D., Henson, S.M., Aspinall, R., Lepperdinger, G., and Grubeck-Loebenstein, B., CD25-expressing CD8 T cells are potent memory cells in old age, J. Immunol., 2005, vol. 175, pp. 1566–1574.

    Article  CAS  PubMed  Google Scholar 

  • Hong, J., Zang, Y.C., Nie, H., and Zhang, J.Z., CD4+ regulatory T cell responses induced by T cell vaccination in patients with multiple sclerosis, Proc. Natl. Acad. Sci. U. S. A., 2006, vol. 103, pp. 5024–5029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huurman, V.A., Decochez, K., Mathieu, C., Cohen, I.R., and Roep, B.O., Therapy with the Hsp60 peptide Dia- Pep277 in C-peptide positive type 1 diabetes patients, Diabetes Metab. Res. Rev., 2007, vol. 23, pp. 269–275.

    Article  CAS  PubMed  Google Scholar 

  • Ilyina, N.A., Kozhevnikov, V.S., Goyman, E.V., Kudaeva, O.T., and Kolesnikova, O.P., The development of a delayed-type hypersensitivity reaction in response to administration of autologous activated cells, Omsk. Nauch. Vestnik, 2007, vol. 3, no. 61, pp. 188–190.

    Google Scholar 

  • Imamichi, H., Lempicki, R.A., Adelsberger, J.W., Hasley, R.B., Rosenberg, A., Roby, G., Rehm, C.A., Nelson, A., Krishnan, S., Pavlick, M., Woods, C.J., Baseler, M.W., and Lane, H.C., The CD8+HLA-DR+ T cells expanded in HIV-1 infection are qualitatively identical to those from healthy controls, Eur. J. Immunol., 2012, vol. 42, pp. 2608–2620.

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann, S.H., Heat shock proteins and the immune response, Immunol. Today, 1990, vol. 11, pp. 129–136.

    Article  CAS  PubMed  Google Scholar 

  • Korolkova, O.Yu., Senyukov, V.V., and Kozhevnikov, V.S., Expression of ergotope-associated markers by activated T-lymphocytes, Med. Immunol., 2009, vol. 11, nos. 2–3, pp. 255–260.

    Google Scholar 

  • Kozhevnikov, V.S., Anti-ergotypic response: theoretical aspects and clinical significance, in Kletochnye tekhnologii: teoreticheskie i prikladnye aspekty (Cell Technologies: Theoretical and Applied Aspects), Novosibirsk: Nauka, 2009, pp. 75–86.

    Google Scholar 

  • Kozlov, V.A., Supressor cells—the basis of immunopathogenesis of autoimmune diseases, Med. Immunol., 2016, vol. 18, no. 1, pp. 7–15.

    Article  Google Scholar 

  • Kurganova, E.V., Shevela, E.Ya., Tikhonova, M.A., Ostanin, A.A., and Chernykh, E.R., In vitro generation and characterization of human regulatory T-cells, Med. Immunol., 2008, vol. 10, nos. 2–3, pp. 173–180.

    Google Scholar 

  • Litvinova, L.S., Gutsol, A.A., Sokhonevich, N.A., Kofanova, K.A., Khaziakhmatova, O.G., Shupletsova, V.V., Kaigorodova, E.V., and Goncharov, A.G., Basic surface markers of functional activity T lymphocytes, Med. Immunol., 2014, vol. 16, no. 1, pp. 7–26.

    Article  Google Scholar 

  • Lohse, A.W., Mor, F., Karin, N., and Cohen, I.R., Control of experimental autoimmune encephalomyelitis by T cells responding to activated T cells, Science, 1989, vol. 244, pp. 820–822.

    Article  CAS  PubMed  Google Scholar 

  • Mimran, A., Mor, F., Carmi, P., Quintana, F.J., Rotter, V., and Cohen, I.R., DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response, J. Clin. Invest., 2004, vol. 113, pp. 924–932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mimran, A., Mor, F., Quintana, F.J., and Cohen, I.R., Anti-ergotypic T cells in naïve rats, J. Autoimmunity, 2005, vol. 24, pp. 191–201.

    Article  CAS  Google Scholar 

  • Quitana, F.J, Mimran, A., Carmi, P., Mor, F., and Cohen, I.R., HSP60 as a target of anti-ergotypic regulatory T cells, PLoS One, 2008, vol. 3, no. 12, p. e4026.

    Article  Google Scholar 

  • Soltys, B.J. and Gupta, R.S., Cell surface localization of the 60 kDa heat shock chaperonin protein (hsp60) in mammalian Cells, Cell. Biol. Int., 1997, vol. 21, pp. 315–320.

    Article  CAS  PubMed  Google Scholar 

  • Trzonkowski, P., Szarynska, M., Mysliwska, J., and Myśliwski, A., Ex vivo expansion of CD4+CD25+ T regulatory cells for immunosuppressive therapy, Cytometry A, 2009, vol. 75, pp. 175–188.

    Article  PubMed  Google Scholar 

  • Wenzel, J., Henze, S., Brahler, S., Bieber, T., and Tuting, T., The expression of human leukocyte antigen-DR and CD25 on circulating T cells in cutaneous lupus erythematosus and correlation with disease activity, Exp. Dermatol., 2005, vol. 14, pp. 454–459.

    Article  CAS  PubMed  Google Scholar 

  • Zanin-Zhorov, A., Nussbaum, G., Franitza, S., Cohen, I.R., and Lider, O., T cells respond to heat shock protein 60 via TLR2: activation of adhesion and inhibition of chemokine receptors, FASEB J., 2003, vol. 17, pp. 1567–1569.

    Article  CAS  PubMed  Google Scholar 

  • Zanin-Zhorov, A., Bruck, R., Tal, G., Oren, S., Aeed, H., Hershkoviz, R., Cohen, I.R., and Lider, O., Heat shock protein 60 inhibits Th1-mediated hepatitis model via innate regulation of Th1/Th2 transcription factors and cytokines, J. Immunol., 2005, vol. 174, pp. 3227–3236.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to E. A. Blinova.

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Original Russian Text © E.A. Blinova, E.A. Pashkina, A.E. Tevs, V.M. Nepomnyashchikh, M.I. Leonova, D.V. Demina, V.A. Kozlov, 2017, published in Tsitologiya, 2017, Vol. 59, No. 6, pp. 428–433.

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Blinova, E.A., Pashkina, E.A., Tevs, A.E. et al. Expression of ergotope-associated markers of T lymphocytes in atopic dermatitis after in vitro polyclonal activation. Cell Tiss. Biol. 11, 434–439 (2017). https://doi.org/10.1134/S1990519X17060025

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  • DOI: https://doi.org/10.1134/S1990519X17060025

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