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Cited by 483

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells

Levings, Megan K., Gregori, Silvia, Tresoldi, Eleonora, Cazzaniga, Sabrina, Bonini, Chiara, Roncarolo, Maria Grazia·2005·Blood
DOI 10.1182/blood-2004-03-1211
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Abstract

Dendritic cells (DCs) are specialized antigen-presenting cells that monitor the antigenic environment and activate naive T cells. The role of DCs is not only to sense danger but also to tolerize the immune system to antigens encountered in the absence of maturation/inflammatory stimuli. Indeed, if a naive T cell encounters its antigen on immature DCs (iDCs), it may differentiate into a T-regulatory (Tr) rather than a T-effector cell. However, little is known about the mechanisms by which iDCs differentiate Tr cells. We developed a standardized and highly reproducible protocol to differentiate Tr cells by repetitive exposure of naive peripheral blood CD4+ T cells to allogeneic iDCs. The resultant Tr cells are phenotypically and functionally identical to type 1 Tr (Tr1) cells because their generation requires production of IL-10 by iDCs, and they suppress T-cell responses through an interleukin-10 (IL-10)– and a transforming growth factor β (TGF-β)–dependent mechanism. In addition, Tr1 cells induced by iDCs do not require the presence of CD4+CD25+ Tr cells for their generation, nor do they express high constitutive levels of CD25 or the transcription factor FoxP3. Thus, iDCs can drive the differentiation of Tr1 cells and can be used to generate large numbers of alloantigen-specific Tr1 cells for clinical use as a cellular therapy to restore peripheral tolerance.

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Research works printed but not linked: 41

  1. Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000; 18: 767-811. · DOI · Paper page
  2. Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 2002; 23: 445-449. · DOI · Paper page
  3. Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol. 2003;21: 685-711. · DOI · Paper page
  4. Akbar AN, Taams LS, Salmon M, Vukmanovic-Stejic M. The peripheral generation of CD4+ CD25+ regulatory T cells. Immunology. 2003; 109: 319-325. · DOI
  5. Shevach EM. CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol. 2002;2: 389-400. · DOI · Paper page
  6. Groux H, O'Garra A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature. 1997;389: 737-742. · DOI · Paper page
  7. Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK. Type 1 T regulatory cells. Immunol Rev. 2001;182: 68-79. · DOI · Paper page
  8. Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med. 1999;190: 995-1004. · DOI · Paper page
  9. Nakamura K, Kitani A, Strober W. Cell contact-dependent immunosuppression by CD4(+) CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med. 2001;194: 629-644. · DOI · Paper page
  10. Levings MK, Sangregorio R, Sartirana C, et al. Human CD25+CD4+ T suppressor cell clones produce TGF-β, but not IL-10 and are distinct from type 1 T regulatory cells. J Exp Med. 2002; 196: 1335-1346. · DOI · Paper page
  11. Dieckmann D, Bruett CH, Ploettner H, Lutz MB, Schuler G. Human CD4(+)CD25(+) regulatory, contact-dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells [corrected]. J Exp Med. 2002;196: 247-253. · DOI · Paper page
  12. Jonuleit H, Schmitt E, Kakirman H, Stassen M, Knop J, Enk AH. Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells. J Exp Med. 2002;196: 255-260. · DOI · Paper page
  13. Foussat A, Cottrez F, Brun V, Fournier N, Breittmayer JP, Groux H. A comparative study between T regulatory type 1 and CD4(+)CD25(+) T cells in the control of inflammation. J Immunol. 2003; 171: 5018-5026. · DOI
  14. Hawiger D, Inaba K, Dorsett Y, et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med. 2001;194: 769-779. · DOI · Paper page
  15. Mahnke K, Qian Y, Knop J, Enk AH. Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood. 2003; 101: 4862-4869. · DOI · Paper page
  16. Probst HC, Lagnel J, Kollias G, van den Broek M. Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity. 2003;18: 713-720. · DOI · Paper page
  17. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med. 2002;196: 1627-1638. · DOI · Paper page
  18. Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med. 2001;193: 233-238. · DOI · Paper page
  19. Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, non-proliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med. 2000; 192: 1213-1222. · DOI · Paper page
  20. Brown JA, Dorfman DM, Ma FR, et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol. 2003;170: 1257-1266. · DOI · Paper page
  21. Corinti S, Albanesi C, la Sala A, Pastore S, Girolomoni G. Regulatory activity of autocrine IL-10 on dendritic cell functions. J Immunol. 2001;166: 4312-4318. · DOI · Paper page
  22. Wing K, Ekmark A, Karlsson H, Rudin A, SuriPayer E. Characterization of human CD25+CD4+ T cells in thymus, cord and adult blood. Immunology. 2002;106: 190-199. · DOI
  23. de La Selle V, Gluckman E, Bruley-Rosset M. Graft-versus-host disease and graft-versus-leukemia effect in mice grafted with peripheral newborn blood. Blood. 1998;92: 3968-3975. · DOI
  24. Levings MK, Sangregorio R, Galbiati F, Squadrone S, de Waal Malefyt R, Roncarolo MG. IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol. 2001; 166: 5530-5539. · DOI · Paper page
  25. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol. 2003;4: 337-342. · DOI · Paper page
  26. Walker MR, Kasprowicz DJ, Gersuk VH, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25– T cells. J Clin Invest. 2003;112: 1437-1443. · DOI · Paper page
  27. Cobbold SP, Castejon R, Adams E, et al. Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants. J Immunol. 2004;172: 6003-6010. · DOI · Paper page
  28. Vieira PL, Christensen JR, Minaee S, et al. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J Immunol. 2004;172: 5986-5993. · DOI · Paper page
  29. Graca L, Cobbold SP, Waldmann H. Identification of regulatory T cells in tolerated allografts. J Exp Med. 2002;195: 1641-1646. · DOI · Paper page
  30. Vlad G, Piazza F, Colovai A, et al. Interleukin-10 induces the upregulation of the inhibitory receptor ILT4 in monocytes from HIV positive individuals. Hum Immunol. 2003;64: 483-489. · DOI
  31. Chang CC, Ciubotariu R, Manavalan JS, et al. Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol. 2002;3: 237-243. · DOI · Paper page
  32. Wakkach A, Fournier N, Brun V, Breittmayer JP, Cottrez F, Groux H. Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity. 2003;18: 605-617. · DOI · Paper page
  33. Steinbrink K, Graulich E, Kubsch S, Knop J, Enk AH. CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood. 2002;99: 2468-2476. · DOI · Paper page
  34. Sato K, Yamashita N, Baba M, Matsuyama T. Regulatory dendritic cells protect mice from murine acute graft-versus-host disease and leukemia relapse. Immunity. 2003;18: 367-379. · DOI · Paper page
  35. Penna G, Adorini L. Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol. 2000; 164: 2405-2411. · DOI · Paper page
  36. McGuirk P, McCann C, Mills KH. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates inter-leukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J Exp Med. 2002;195: 221-231. · DOI · Paper page
  37. Gray CP, Arosio P, Hersey P. Heavy chain ferritin activates regulatory T cells by induction of changes in dendritic cells. Blood. 2002;99: 3326-3334. · DOI · Paper page
  38. Hackstein H, Morelli AE, Thomson AW. Designer dendritic cells for tolerance induction: guided not misguided missiles. Trends Immunol. 2001;22: 437-442. · DOI
  39. Lu L, Bonham CA, Liang X, et al. Liver-derived DEC205+B220+CD19– dendritic cells regulate T cell responses. J Immunol. 2001;166: 7042-7052. · DOI
  40. Gilliet M, Liu YJ. Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med. 2002;195: 695-704. · DOI · Paper page
  41. Roncarolo MG, Levings MK, Traversari C. Differentiation of T regulatory cells by immature dendritic cells. J Exp Med. 2001;193: F5-F10. · DOI · Paper page

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Metadata

Authors
Levings, M. K., Gregori, S., Tresoldi, E., Cazzaniga, S., Bonini, C., & Roncarolo, M. G.
Venue
Blood
Publisher
American Society of Hematology
Published
2005-02-01
Volume
105
Issue
3
Pages
1162-1169
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2004-03-1211
OpenAlex
W2082992807
Cited by
483
References
2
FWCI
12.68
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. https://app.cochat.ai/papers/10.1182/blood-2004-03-1211
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Levings, M. K., Gregori, S., Tresoldi, E., Cazzaniga, S., Bonini, C., & Roncarolo, M. G. (2005). Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood. https://doi.org/10.1182/blood-2004-03-1211

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