Blockade of CD122 on memory T cells in the skin suppresses sclerodermatous graft-versus-host disease.

Antigen-stimulated naïve T cells differentiate into effector and memory T cells, of which resident memory T (TRM) cells reside permanently in organ tissues. Involvement of TRM cells has been indicated in pathological conditions of various skin diseases. CD122, which is the β chain subunit of interleukin (IL)- 2 and IL-15 receptors, is expressed on immune cells including TRM cells. To investigate whether CD122 signaling in skin CD8+ TRM cells mediates the development of mucocutaneous graft-versus-host disease (GVHD). We used a genetically modified mouse expressing a membrane-bound form of chicken ovalbumin (OVA) under the control of the keratin 14 promoter, which develops GVHD-like erosive mucocutaneous disease resulting in sclerodermatous disease after transfer of OVA-specific T cell-receptor-transgenic CD8+ OT-I cells. Mice with mucocutaneous GVHD were treated with an anti-CD122 blocking antibody. Administration of an anti-CD122 blocking antibody suppresses the development of acute/chronic GVHD-like mucocutaneous disease in our murine model via the reduction of CD122-expressing memory CD8+ T cells, including skin, memory autoaggressive CD8+ T cells. Moreover, blockade of CD122, even after the establishment of acute GVHD, inhibited the development of chronic GVHD-like sclerodermatous disease via the reduction of epidermal and dermal TRM autoaggressive CD8+ T cells. Skin memory CD8+ T cells in particular mediate the development of mucocutaneous GVHD, and blockade of CD122 may be an effective treatment strategy, especially for sclerodermatous GVHD. Copyright © 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Citation

Noriko Kubota, Ryota Tanaka, Yuki Ichimura, Risa Konishi, J Yun Tso, Naoya Tsurushita, Toshifumi Nomura, Naoko Okiyama. Blockade of CD122 on memory T cells in the skin suppresses sclerodermatous graft-versus-host disease. Journal of dermatological science. 2023 Mar;109(3):127-135

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PMID: 36966029

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