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MHC 类 Ib 限制性 CD8 T 细胞具有强大的杀瘤活性。

MHC class Ib-restricted CD8 T cells possess strong tumoricidal activities.

机构信息

Chinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

The Third Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, Suzhou, Jiangsu 215123, China.

出版信息

Proc Natl Acad Sci U S A. 2023 Oct 24;120(43):e2304689120. doi: 10.1073/pnas.2304689120. Epub 2023 Oct 19.

DOI:10.1073/pnas.2304689120
PMID:37856544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10614629/
Abstract

The importance of classical CD8 T cells in tumor eradication is well acknowledged. However, the anti-tumor activity of MHC (major histocompatibility complex) Ib-restricted CD8 T (Ib-CD8 T) cells remains obscure. Here, we show that CX3CR1-expressing Ib-CD8 T cells (Ib-restricted CD8 T cells) highly express cytotoxic factors, austerely resist exhaustion, and effectively eliminate various tumors. These Ib-CD8 T cells can be primed by MHC Ia (MHC class Ia molecules) expressed on various cell types for optimal activation in a Tbet-dependent manner. Importantly, MHC Ia does not allogeneically activate Ib-CD8 T cells, rather, sensitizes these cells for T cell receptor activation. Such effects were observed when MHC Ia cells were administered to tumor-bearing KDmice. A similar population of tumoricidal CX3CR1CD8 T cells was identified in wild-type mice and melanoma patients. Adoptive transfer of Ib-CD8 T cells to wild-type mice inhibited tumor progression without damaging normal tissues. Taken together, we demonstrate that MHC class Ia can prime Ib-CD8 T cells for robust tumoricidal activities.

摘要

经典 CD8 T 细胞在肿瘤清除中的重要性已得到充分认可。然而，MHC（主要组织相容性复合体）Ib 限制的 CD8 T（Ib-CD8 T）细胞的抗肿瘤活性仍不清楚。在这里，我们表明表达 CX3CR1 的 Ib-CD8 T 细胞（Ib 限制的 CD8 T 细胞）高度表达细胞毒性因子，严格抵抗衰竭，并有效消除各种肿瘤。这些 Ib-CD8 T 细胞可通过 MHC Ia（MHC I 类分子）在各种细胞类型上表达进行初始激活，以 Tbet 依赖性方式进行最佳激活。重要的是，MHC Ia 不会同种异体激活 Ib-CD8 T 细胞，而是使这些细胞对 T 细胞受体激活敏感。当 MHC Ia 细胞给予荷瘤 KD 小鼠时，观察到这种效应。在野生型小鼠和黑色素瘤患者中也鉴定出了类似的杀伤性 CX3CR1CD8 T 细胞群。将 Ib-CD8 T 细胞过继转移至野生型小鼠可抑制肿瘤进展而不损伤正常组织。综上所述，我们证明 MHC I 类可对 Ib-CD8 T 细胞进行初始激活以发挥强大的抗肿瘤活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/9f25e34cc962/pnas.2304689120fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/75d9c01662d9/pnas.2304689120fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/6558b97c51ea/pnas.2304689120fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/ead35e42b622/pnas.2304689120fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/31c44aa21db5/pnas.2304689120fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/fc7f8c24f9dd/pnas.2304689120fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/567327dcd9a5/pnas.2304689120fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/9f25e34cc962/pnas.2304689120fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/75d9c01662d9/pnas.2304689120fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/6558b97c51ea/pnas.2304689120fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/ead35e42b622/pnas.2304689120fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/31c44aa21db5/pnas.2304689120fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/fc7f8c24f9dd/pnas.2304689120fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/567327dcd9a5/pnas.2304689120fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3310/10614629/9f25e34cc962/pnas.2304689120fig07.jpg

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