Journal article
Transfer of Tolerance to Collagen Type V Suppresses T-Helper-Cell-17 Lymphocyte-Mediated Acute Lung Transplant Rejection
Transplantation, Vol.88(12), pp.1341-1348
12/27/2009
DOI: 10.1097/TP.0b013e3181bcde7b
PMCID: PMC2804859
PMID: 20029330
Abstract
Background. Rat lung allograft rejection is mediated by collagen type V (col(V)) specific T-helper-cell 17 (Th 17) cells. Adoptive transfer of these cells is sufficient to induce rejection pathology in isografts, whereas tolerance to col(V) suppresses allograft rejection. Therefore, we tested whether regulatory T cells from tolerant rats Could suppress the Th17-mediated rejection in the syngeneic model of lung transplantation.
Methods. Rats were subjected to syngeneic left lung transplantation, and acute rejection was induced by adoptive transfer of lymph node cells from col(V)-immunized rats. Tolerance was induced by intravenous injection of col(V), and spleen lymphocytes were used for adoptive transfer. CD4(+) T cells were depleted using magnetic beads. Lung isografts were analyzed using micro-positron emission tomography imaging and histochemistry. The transvivo delayed type hypersensitivity assay was used to analyze the Th17 response.
Results. Adoptive cotransfer of col(V)-specific effector cells with cells from col(V)-tolerized rats suppressed severe vasculitis and bronchiolitis with parenchymal inflammation, and the expression of interleukin (IL)- 17 transcripts in mediastinal lymph nodes induced by effector cells alone. Analysis by transvivo delayed type hypersensitivity showed that the reactivity to col(V) was dependent on the presence Of tumor necrosis factor-alpha and IL-17 but not interferon-gamma. Depletion of CD4(+) T cells from the suppressor cell population abrogated the col(V)-specific protection.
Conclusion. Th17-mediated acute rejection after lung transplantation is ameliorated by CD4(+) col(V)-specific regulatory T cells. The mechanism for this Th 17 Suppression is consistent with tolerance induction to col(V). The goal of transplantation treatment, therefore, should target Th17 development and not suppression of T-cell activation by suppressing IL-2.
Details
- Title: Subtitle
- Transfer of Tolerance to Collagen Type V Suppresses T-Helper-Cell-17 Lymphocyte-Mediated Acute Lung Transplant Rejection
- Creators
- Ruedi K. Braun - Loyola Univ, Med Ctr, Dept Thorac & Cardiovasc Surg, Maywood, IL 60153 USAMelanie Molitor-Dart - University of Wisconsin–MadisonChristopher Wigfield - Loyola University ChicagoZhuzai Xiang - University of Wisconsin–MadisonSean B. Fain - University of Wisconsin–MadisonEwa Jankowska-Gan - University of Wisconsin–MadisonChristine M. Seroogy - University of Wisconsin–MadisonWilliam J. Burlingham - University of Wisconsin–MadisonDavid S. Wilkes - Indiana UniversityDavid D. Brand - University of Tennessee Health Science CenterJose Torrealba - University of Wisconsin–MadisonRobert B. Love - Loyola University Chicago
- Resource Type
- Journal article
- Publication Details
- Transplantation, Vol.88(12), pp.1341-1348
- DOI
- 10.1097/TP.0b013e3181bcde7b
- PMID
- 20029330
- PMCID
- PMC2804859
- NLM abbreviation
- Transplantation
- ISSN
- 0041-1337
- eISSN
- 1534-6080
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 8
- Grant note
- R01HL060797 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) HL60797; HL/Al67177 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 12/27/2009
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Health, Sport, and Human Physiology
- Record Identifier
- 9984274957702771
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