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Host-Derived Langerhans Cells Persist after MHC-Matched Allografting Independent of Donor T Cells and Critically Influence the Alloresponses Mediated by Donor Lymphocyte Infusions

Nadira Durakovic, Karl B. Bezak, Mario Skarica, Vedran Radojcic, Ephraim J. Fuchs, George F. Murphy and Leo Luznik
J Immunol October 1, 2006, 177 (7) 4414-4425; DOI: https://doi.org/10.4049/jimmunol.177.7.4414
Nadira Durakovic
*Divisions of Hematologic Malignancies and Cancer Immunology and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231; and
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Karl B. Bezak
*Divisions of Hematologic Malignancies and Cancer Immunology and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231; and
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Mario Skarica
*Divisions of Hematologic Malignancies and Cancer Immunology and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231; and
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Vedran Radojcic
*Divisions of Hematologic Malignancies and Cancer Immunology and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231; and
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Ephraim J. Fuchs
*Divisions of Hematologic Malignancies and Cancer Immunology and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231; and
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George F. Murphy
†Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
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Leo Luznik
*Divisions of Hematologic Malignancies and Cancer Immunology and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231; and
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Abstract

Mouse models of minor histocompatibility Ag-mismatched bone marrow transplantation were used to study donor dendritic cell (DC) reconstitution after conditioning, variables influencing the persistence of residual host DCs in different compartments, their phenotype, and their role in governing donor lymphocyte infusion (DLI)-mediated alloresponses. Reconstitution of all splenic DC subsets occurred rapidly after bone marrow transplantation and before T cell reconstitution. However, in contrast to MHC-mismatched chimeras, residual host-derived DCs persisted in the cutaneous lymph nodes (CLNs) of MHC-matched chimeras despite the presence or addition of donor T cells to the graft. The phenotype of these residual host-derived DCs in CLNs was consistent with Langerhans’ cells (LCs). We confirmed their skin origin and found near-complete preservation of host-derived LCs in the skin. Host-derived LCs retained their ability to continuously traffic to the CLNs, expressed homogeneously increased levels of costimulatory molecules, and could capture and carry epicutaneously applied Ags. To determine the role of residual host LCs in governing DLI-mediated alloresponses, we administered DLI alone or after topical application of the TLR7 ligand imiquimod, which is known to enhance the LC emigration from the skin. DLI administration resulted in a decrease in host-derived DCs in the CLNs and increased recruitment of donor-derived DCs to the skin, whereas imiquimod augmented their alloreactivity. These results suggest uniqueness of the MHC-matched setting in relation to the persistence of host-derived DCs in the skin and points to a previously unrecognized role of host-derived LCs in the induction of DLI-mediated graft-vs-host alloresponses.

  • Received July 19, 2005.
  • Accepted July 17, 2006.
  • Copyright © 2006 by The American Association of Immunologists
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The Journal of Immunology: 177 (7)
The Journal of Immunology
Vol. 177, Issue 7
1 Oct 2006
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Host-Derived Langerhans Cells Persist after MHC-Matched Allografting Independent of Donor T Cells and Critically Influence the Alloresponses Mediated by Donor Lymphocyte Infusions
Nadira Durakovic, Karl B. Bezak, Mario Skarica, Vedran Radojcic, Ephraim J. Fuchs, George F. Murphy, Leo Luznik
The Journal of Immunology October 1, 2006, 177 (7) 4414-4425; DOI: 10.4049/jimmunol.177.7.4414

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Host-Derived Langerhans Cells Persist after MHC-Matched Allografting Independent of Donor T Cells and Critically Influence the Alloresponses Mediated by Donor Lymphocyte Infusions
Nadira Durakovic, Karl B. Bezak, Mario Skarica, Vedran Radojcic, Ephraim J. Fuchs, George F. Murphy, Leo Luznik
The Journal of Immunology October 1, 2006, 177 (7) 4414-4425; DOI: 10.4049/jimmunol.177.7.4414
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