Langerhans Cells Suppress CD8+ T Cells In Situ during Mucocutaneous Acute Graft-Versus-Host Disease.

Abstract

Acute graft-versus-host disease (aGVHD) induced by allogenic hematopoietic stem cell transplantation is an immunological disorder in which donor lymphocytes attack recipient organs. It has been proven that recipient nonhematopoietic tissue cells, such as keratinocytes, are sufficient as immunological targets for allogenic donor T cells, whereas Langerhans cells (LCs) are potent professional hematopoietic antigen-presenting cells existing in the target epidermis and eliminated during the early phase of mucocutaneous aGVHD. Moreover, LCs have been reported to negatively regulate various types of immune responses. Here, we present data showing that initial depletion of recipient LCs exacerbates mucocutaneous lesions in a murine model of allogenic bone marrow transplantation-induced aGVHD. Furthermore, another murine model of mucocutaneous aGVHD induced in mice with keratinocytes genetically expressing chicken ovalbumin by transfer of ovalbumin-specific CD8+ OT-I cells also showed that LC-depleted recipient mice develop aggravated mucocutaneous disease owing to decreased apoptosis of skin-infiltrating OT-I cells. Moreover, coexisting LCs directly induce apoptosis and inhibit the proliferation of OT-I cells in vitro partially via B7 family proteins. Collectively, our results indicate that LCs negatively regulate mucocutaneous aGVHD-like lesions in situ by inhibiting the number of infiltrating CD8+ T cells.

• Authors: Noriko Kubota, Akimasa Saito, Ryota Tanaka, Yoshiyuki Nakamura, Rei Watanabe, Yasuhiro Fujisawa, Yosuke Ishitsuka, Björn E Clausen, Manabu Fujimoto, Naoko Okiyama
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 141 Issue 5 Pg. 1177-1187.e3 (05 2021) ISSN: 1523-1747 [Electronic] United States
• PMID: 33091425 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• B7 Antigens
• Cd276 protein, mouse
• V-Set Domain-Containing T-Cell Activation Inhibitor 1
• Vtcn1 protein, mouse

Topics

• Acute Disease
• Animals
• Apoptosis
• B7 Antigens (physiology)
• Bone Marrow Transplantation (adverse effects)
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Graft vs Host Disease (immunology)
• Langerhans Cells (physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Skin Diseases (immunology)
• V-Set Domain-Containing T-Cell Activation Inhibitor 1 (physiology)