表皮内ニッチをめぐる競合が，抗原特異的T細胞保存の選択圧として働く

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  • 平井 敏郎
    大阪大学先導的学際研究機構/微生物病研究所BIKEN次世代ワクチン協働研究所 大阪大学大学院薬学研究科

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タイトル別名
  • Competition between T Cells for a Finite Epidermal Niche Promotes Selective Retention of Antigen-specific Memory T Cells in the Epidermis
  • ヒョウヒ ナイ ニッチ オ メグル キョウゴウ ガ,コウゲン トクイテキ Tサイボウ ホゾン ノ センタクアツ ト シテ ハタラク

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<p>Tissue-resident memory T cells are a highly abundant, non-blood circulating subset of memory T cells. These appear to be the most protective population of memory T cells at barrier surfaces. Long-term retention and survival of tissue-resident memory CD8+ T cells (Trm) is determined by tissue-derived signals, such as keratinocyte-mediated activation of transforming growth factor β (TGFβ) in the epidermis. We found that T cell clones compete for limited amounts of active TGFβ and pre-existing Trm could be replaced with newly recruited effector T cells in the epidermis. On the other hand, when effector T cells transition into Trm, the presence of cutaneous cognate antigen increases the fitness of individual Trm clones in the epidermal niche. Thus, antigen-specific Trm are more efficiently retained than bystander Trm that have not encountered cognate antigens when they compete with newly recruited effector T cells for limited active TGFβ. Therefore, competition between T cells for active TGFβ represents a selective pressure that promotes the accumulation of antigen-specific Trm cells in the epidermal niche. Furthermore, our model implies that the epidermis offers a finite niche for maintaining Trm. Although the epidermal niche of Trm cannot represent the capacity of T cell-mediated immune memory in our body, these findings might suggest a challenge for the accommodation of memory T cells specific to multiple pathogens throughout a lifetime.</p>

収録刊行物

  • 薬学雑誌

    薬学雑誌 142 (12), 1327-1332, 2022-12-01

    公益社団法人 日本薬学会

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