Maintenance of immune tolerance depends on normal tissue homeostasis

Zita F. H. M. Boonman, Geertje J. D. van Mierlo, Marieke F. Fransen, Rob J. W. de Keizer, Martine J. Jager, Cornelis J. M. Melief, René E. M. Toes

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Ags expressed at immune privileged sites and other peripheral tissues are able to induce T cell tolerance. In this study, we analyzed whether tolerance toward an intraocular tumor expressing a highly immunogenic CTL epitope is maintained, broken, or reverted into immunity in the event the anatomical integrity of the eye is lost. Inoculation of tumor cells into the anterior chamber of the eye of naive B6 mice leads to progressive intraocular tumor growth, an abortive form of CTL activation in the tumor-draining subrnandibular lymph node, and systemic tolerance as evidenced by the inability of these mice to reject an otherwise benign tumor cell inoculum. Loss of anatomical integrity of the eye as a consequence of phthisis resulted in loss of systemic tolerance and the emergence of effective antitumor immunity against an otherwise lethal tumor challenge. Phthisis was accompanied by dendritic cell maturation and preceded the induction of systemic tumor-specific CTL immunity. Our data show that normal tissue homeostasis and anatomical integrity is required for the maintenance of ocular tolerance and prevention of CTL-mediated immunity. These data also indicate that tissue injury in the absence of viral or microbial infection can act as a switch for the induction of CTL immunity. Copyright © 2005 by The American Association of Immunologists, Inc.
Original languageEnglish
Pages (from-to)4247-4254
JournalJournal of Immunology
Volume175
Issue number7
DOIs
Publication statusPublished - 2005
Externally publishedYes

Cite this

Boonman, Z. F. H. M., van Mierlo, G. J. D., Fransen, M. F., de Keizer, R. J. W., Jager, M. J., Melief, C. J. M., & Toes, R. E. M. (2005). Maintenance of immune tolerance depends on normal tissue homeostasis. Journal of Immunology, 175(7), 4247-4254. https://doi.org/10.4049/jimmunol.175.7.4247
Boonman, Zita F. H. M. ; van Mierlo, Geertje J. D. ; Fransen, Marieke F. ; de Keizer, Rob J. W. ; Jager, Martine J. ; Melief, Cornelis J. M. ; Toes, René E. M. / Maintenance of immune tolerance depends on normal tissue homeostasis. In: Journal of Immunology. 2005 ; Vol. 175, No. 7. pp. 4247-4254.
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abstract = "Ags expressed at immune privileged sites and other peripheral tissues are able to induce T cell tolerance. In this study, we analyzed whether tolerance toward an intraocular tumor expressing a highly immunogenic CTL epitope is maintained, broken, or reverted into immunity in the event the anatomical integrity of the eye is lost. Inoculation of tumor cells into the anterior chamber of the eye of naive B6 mice leads to progressive intraocular tumor growth, an abortive form of CTL activation in the tumor-draining subrnandibular lymph node, and systemic tolerance as evidenced by the inability of these mice to reject an otherwise benign tumor cell inoculum. Loss of anatomical integrity of the eye as a consequence of phthisis resulted in loss of systemic tolerance and the emergence of effective antitumor immunity against an otherwise lethal tumor challenge. Phthisis was accompanied by dendritic cell maturation and preceded the induction of systemic tumor-specific CTL immunity. Our data show that normal tissue homeostasis and anatomical integrity is required for the maintenance of ocular tolerance and prevention of CTL-mediated immunity. These data also indicate that tissue injury in the absence of viral or microbial infection can act as a switch for the induction of CTL immunity. Copyright {\circledC} 2005 by The American Association of Immunologists, Inc.",
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Boonman, ZFHM, van Mierlo, GJD, Fransen, MF, de Keizer, RJW, Jager, MJ, Melief, CJM & Toes, REM 2005, 'Maintenance of immune tolerance depends on normal tissue homeostasis' Journal of Immunology, vol. 175, no. 7, pp. 4247-4254. https://doi.org/10.4049/jimmunol.175.7.4247

Maintenance of immune tolerance depends on normal tissue homeostasis. / Boonman, Zita F. H. M.; van Mierlo, Geertje J. D.; Fransen, Marieke F.; de Keizer, Rob J. W.; Jager, Martine J.; Melief, Cornelis J. M.; Toes, René E. M.

In: Journal of Immunology, Vol. 175, No. 7, 2005, p. 4247-4254.

Research output: Contribution to journalArticleAcademicpeer-review

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AB - Ags expressed at immune privileged sites and other peripheral tissues are able to induce T cell tolerance. In this study, we analyzed whether tolerance toward an intraocular tumor expressing a highly immunogenic CTL epitope is maintained, broken, or reverted into immunity in the event the anatomical integrity of the eye is lost. Inoculation of tumor cells into the anterior chamber of the eye of naive B6 mice leads to progressive intraocular tumor growth, an abortive form of CTL activation in the tumor-draining subrnandibular lymph node, and systemic tolerance as evidenced by the inability of these mice to reject an otherwise benign tumor cell inoculum. Loss of anatomical integrity of the eye as a consequence of phthisis resulted in loss of systemic tolerance and the emergence of effective antitumor immunity against an otherwise lethal tumor challenge. Phthisis was accompanied by dendritic cell maturation and preceded the induction of systemic tumor-specific CTL immunity. Our data show that normal tissue homeostasis and anatomical integrity is required for the maintenance of ocular tolerance and prevention of CTL-mediated immunity. These data also indicate that tissue injury in the absence of viral or microbial infection can act as a switch for the induction of CTL immunity. Copyright © 2005 by The American Association of Immunologists, Inc.

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Boonman ZFHM, van Mierlo GJD, Fransen MF, de Keizer RJW, Jager MJ, Melief CJM et al. Maintenance of immune tolerance depends on normal tissue homeostasis. Journal of Immunology. 2005;175(7):4247-4254. https://doi.org/10.4049/jimmunol.175.7.4247