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Graft-versus-Host Disease

Induction of recipient cell-specific donor T-cell anergy by UV-C-irradiated recipient immature monocyte-derived dendritic cells

Bone Marrow Transplantation volume 41, pages 1037–1045 (2008)Cite this article

Abstract

The induction of donor T-cell anergy to recipient cells for reducing GVHD could be one way of expanding donor candidates for HLA-mismatched hematopoietic SCT. The present study was designed to clarify whether recipient cell-specific T-cell anergy could be induced by priming donor lymphocytes with recipient monocyte-derived DCs (mo-DCs) irradiated with ultraviolet-C (UV-C). By irradiation of mo-DCs with UV-C, the expression of DC-associated surface phenotypes such as CD83, CD80, CD86 and CD40 was reduced and the antigen-presenting ability of UV-C-irradiated mo-DCs was clearly decreased. By co-culturing normal donor 1 lymphocytes with UV-C-irradiated donor 2 immature mo-DCs, the response of the lymphocytes to donor 2 mature mo-DCs was markedly reduced as compared with that of the lymphocytes prestimulated with non-irradiated donor 2 immature mo-DCs or UV-C-irradiated mo-DCs derived from a different individual donor 3. The present study demonstrated that recipient cell-specific T-cell anergy could be induced by priming donor lymphocytes with UV-C-irradiated recipient immature mo-DCs in hematopoietic SCT. These data suggest the applicability of donor graft cells, which have been prestimulated with UV-C-irradiated recipient immature mo-DCs, for expanding donor candidates in HLA-mismatched hematopoietic SCT.

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References

  1. Trevisan A, Piovesan S, Leonardi A, Bertocco M, Nicolosi P, Pelizzo MG et al. Unusual high exposure to ultraviolet-C irradiation. Photochem Photobiol 2006; 82: 1077–1079.

    Article  CAS  PubMed  Google Scholar 

  2. Brown Jr IW, Moor GF, Hummel BW, Marshall Jr WG, Collins JP . Toward further reducing wound infections in cardiac operations. Ann Thorac Surg 1996; 62: 1783–1789.

    Article  PubMed  Google Scholar 

  3. Rattis FM, Peguet-Navarro J, Courtellemont P, Redziniak G, Schmitt D . In vitro effects of ultraviolet B irradiation on human Langerhans cell antigen-presenting function. Cell Immunol 1995; l64: 65–72.

    Article  Google Scholar 

  4. Simon JC, Tigelaar RE, Bergstresser PR, Edelbaum D, Cruz Jr PD . Ultraviolet B irradiation converts Langerhans cells from immunogenic to tolerogenic antigen-presenting cells. Induction of specific clonal anergy in CD4+ T helper 1 cells. J Immunol 1991; 146: 485–491.

    CAS  PubMed  Google Scholar 

  5. Simon JC, Cruz Jr PD, Bergstresser PR, Tigelaar R . Low dose ultraviolet B-irradiated Langerhans cells preferentially activate CD4+ cells of the T helper 2 subset. J Immunol 1990; 145: 2087–2091.

    CAS  PubMed  Google Scholar 

  6. Streilein JW, Taylor JR, Vincek V, Kurimoto I, Shimizu T, Tie C et al. Immune surveillance and sunlight-induced skin cancer. Immunol Today 1994; 15: l74–179.

    Article  Google Scholar 

  7. Cooper KD, Oberhelman L, Hamilton TA, Baadsgaard O, Terhune M, Levee G et al. UV exposure reduces immunization rates and promotes tolerance to epicutaneous antigens in humans: relationship to dose, CDla DR+ epidermal macrophage induction, and Langerhans cell depletion. Proc Natl Acad Sci USA 1992; 89: 8497–8501.

    Article  CAS  PubMed  Google Scholar 

  8. Denfeld RW, Hara H, Tesmann JP, Martin S, Simon JC . UVB-irradiated DC are impaired in their APC function and tolerize primed Thl cells but not naive CD4+ T cells. J Leukoc Biol 2001; 69: 548–554.

    CAS  PubMed  Google Scholar 

  9. Osman Y, Takahashi M, Zheng Z, Koike T, Toba K, Liu A et al. Generation of bcr-abl specific cytotoxic T-lymphocytes by using DC pulsed with bcr-abl (b3a2) peptide: its applicability for donor leukocyte transfusions in marrow grafted CML patients. Leukemia 1999; 13: 166–174.

    Article  CAS  Google Scholar 

  10. Zheng Z, Takahashi M, Toba K, Liu A, Furukawa T, Koike T et al. Generation of DC from adherent cells of cord blood by culture with GM-CSF, IL-4 and TNF-α. J Hematother Stem Cell Res 2000; 9: 445–456.

    Article  Google Scholar 

  11. Ullrich SE . Modulation of immunity by ultraviolet irradiation: key effects on antigen presentation. J Invest Dermatol 1995; 105: 30–36.

    Article  Google Scholar 

  12. Toews GB, Bergstresser PR, Streilein JW . Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB. J Immunol 1980; 124: 445–453.

    CAS  PubMed  Google Scholar 

  13. Cruz Jr PD, Nixon-Fulton J, Tigelaar RE, Bergstresser PR . Disparate effects of in vitro low-dose UVB irradiation on intravenous immunization with purified epidermal cell subpopulations for the induction of contact hypersensitivity. J Invest Dermatol 1989; 92: 160–165.

    Article  PubMed  Google Scholar 

  14. Grewe M, Gyufko K, Krutmann J . Interleukin-10 production by cultured human keratinocytes: regulation by ultraviolet B and ultraviolet Al irradiation. J Invest Dermatol 1995; 104: 3–6.

    Article  CAS  PubMed  Google Scholar 

  15. Shreedhar V, Giese T, Sung VW, Ullrich SE . A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression. J Immunol 1998; 160: 3783–3789.

    CAS  PubMed  Google Scholar 

  16. Kitazawa T, Streilein JW . Studies on delayed systemic effects of ultraviolet B irradiation on the induction of contact hypersensitivity, 3. Dendritic cells from secondary lymphoid organs are deficient in interleukin-12 production and capacity to promote activation and differentiation of T helper type 1 cells. Immunology 2000; 99: 296–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schwarz A, Grabbe S, Grosse-Heitmeyer K, Roters B, Riemann H, Luger TA et al. Ultraviolet light-induced immune tolerance is mediated via the Fas/Fas-ligand system. J Immunol 1998; 160: 4262–4270.

    CAS  PubMed  Google Scholar 

  18. Bacci S, Nakamura T, Streilein JW . Failed antigen presentation after UVB irradiation correlates with modifications of Langerhans cell cytoskeleton. J Invest Dermatol 1996; l07: 838–843.

    Article  Google Scholar 

  19. Simon JC, Tigelaar RE, Bergstresser PR, Edelbaum D, Cruz Jr PD . Ultraviolet B radiation converts Langerhans cells from immunogenic to tolerogenic antigen-presenting cells. Induction of specific clonal anergy in CD4+ T helper 1 cells. J Immunol 1991; 114: 485–491.

    Google Scholar 

  20. Denfeld RW, Hara H, Tesmann JP, Martin S, Simon JC . UVB-irradiated DC are impaired in their APC function and tolerize primed Thl cells but not naive CD4+ T cells. J Leukoc Biol 2001; 69: 548–554.

    CAS  PubMed  Google Scholar 

  21. Rattis FM, Concha M, Dalbiez-Gauthier C, Courtellemont P, Schmitt D, Peguet-Navarro J . Effects of ultraviolet B irradiation on human Langerhans cells: functional alteration of CD86 upregulation and induction of apoptotic cell death. J Invest Dermatol 1998; 111: 373–379.

    Article  CAS  PubMed  Google Scholar 

  22. Everson MP, Spalding DM, Koopman WJ . Exquisite sensitivity of DC to ultraviolet irradiation and temperature changes. Transplantation 1989; 48: 666–671.

    CAS  PubMed  Google Scholar 

  23. Narita M, Takahashi M, Liu A, Nikkuni K, Furukawa T, Toba K et al. Leukemia blasts-induced T cell anergy demonstrated by leukemia derived dendritic cells in acute myelogenous leukemia. Exp Hematol 2001; 29: 709–719.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan

    N Tochiki, M Narita, C Lu, A Saitoh, N Watanabe, N Satoh & M Takahashi

  2. Division of Hematology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan

    Z Zheng, T Furukawa, K Toba, I Fuse & Y Aizawa

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  1. N Tochiki
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  2. M Narita
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  8. T Furukawa
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  11. Y Aizawa
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Correspondence to M Takahashi.

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Tochiki, N., Narita, M., Zheng, Z. et al. Induction of recipient cell-specific donor T-cell anergy by UV-C-irradiated recipient immature monocyte-derived dendritic cells. Bone Marrow Transplant 41, 1037–1045 (2008). https://doi.org/10.1038/bmt.2008.28

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