Donor helper innate lymphoid cells are replaced earlier than lineage positive cells and persist long-term in human intestinal grafts – a descriptive study
Corresponding Author
Elena Gómez-Massa
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
Correspondence
Elena Gómez-Massa, Avenida de Córdoba s/n, 28041, Madrid, Spain.
Tel.: +34 917792756;
fax: +34 917792756;
e-mail: [email protected]
Search for more papers by this authorMaría Lasa-Lázaro
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorFrancisco Javier Gil-Etayo
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorEsperanza Ulloa-Márquez
Department of Gastroenterology, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorIago Justo
HPB Surgery and Abdominal Transplantation Unit, General Surgery Service, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorCarmelo Loinaz
HPB Surgery and Abdominal Transplantation Unit, General Surgery Service, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorJorge Calvo-Pulido
HPB Surgery and Abdominal Transplantation Unit, General Surgery Service, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorEstela Paz-Artal
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
School of Medicine, Complutense University, Madrid, Spain
Section of Immunology, San Pablo CEU University, Madrid, Spain
Search for more papers by this authorPaloma Talayero
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorCorresponding Author
Elena Gómez-Massa
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
Correspondence
Elena Gómez-Massa, Avenida de Córdoba s/n, 28041, Madrid, Spain.
Tel.: +34 917792756;
fax: +34 917792756;
e-mail: [email protected]
Search for more papers by this authorMaría Lasa-Lázaro
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorFrancisco Javier Gil-Etayo
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorEsperanza Ulloa-Márquez
Department of Gastroenterology, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorIago Justo
HPB Surgery and Abdominal Transplantation Unit, General Surgery Service, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorCarmelo Loinaz
HPB Surgery and Abdominal Transplantation Unit, General Surgery Service, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorJorge Calvo-Pulido
HPB Surgery and Abdominal Transplantation Unit, General Surgery Service, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorEstela Paz-Artal
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
School of Medicine, Complutense University, Madrid, Spain
Section of Immunology, San Pablo CEU University, Madrid, Spain
Search for more papers by this authorPaloma Talayero
Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain
Imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
Search for more papers by this authorSummary
Intestinal grafts carry large donor lymphoid load that is replaced by recipient cells. The dynamics of this process may influence the tolerance, rejection or graft-versus-host disease. We analysed distribution and turnover of T and B (Lin+) lymphocytes, natural killer (NK) and helper innate lymphoid cells (hILC) in intestinal epithelium (IEp) and lamina propia (LP) from a long-term cohort of eight intestinal recipients and from a single patient monitored deeply during the first 8 months post-transplant (posTx). Long-term intestinal grafts showed significantly higher %hILC than native bowels in IEp and LP until 10 years posTx and recovery to normal levels was observed afterwards. We also observed an imbalance between hILC subsets in IEp [increase of type 1 (ILC1) and decrease in type 3 (ILC3) innate lymphoid cells] that persisted along posTx time even when %hILC was similar to native bowels. Regarding hILC origin, we still detected the presence of donor cells at 13 years posTx. However, this chimerism was significantly lower than in Lin+ and NK populations. According to these findings, observation from the patient monitored in early posTx period showed that recipient hILC repopulate earlier and faster than Lin+ cells, with increase in ILC1 related to rejection and infection episodes.
Conflicts of interest
The authors of this manuscript have no conflicts of interest to disclose.
Supporting Information
Filename | Description |
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tri13609-sup-0001-Supinfo.pdfPDF document, 902 KB |
Table S1. Monoclonal antibodies (MAb) used in the study. Table S2. HLA typing from recipients and donors. Figure S1. Representative flow cytometry dot plots for chimerism analysis of intestinal grafts. Figure S2. Blood lymphoid populations in transplanted patients versus healthy controls. Figure S3. Statistical analysis of IEL and LPL populations according to immunosuppressive therapy. Figure S4. Frequency of recipient and donor hILC subsets (ILC1 and ILC3) in IEp and LP from patients P1–P8. Figure S5. Macrochimerism was detected during the first month posTx in patient P9. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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