Differential mechanisms of memory CD8 T cell maintenance by individual myeloid cell types

Journal of Leukocyte Biology

Kimberly S. Schluns¹  Loredana Frasca¹  Spencer W. Stonier¹  Willem W. Overwijk² 

[1] Departments of Immunology and Departments of Immunology and Departments of Immunology and;Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

关键词: homeostasis;    dendritic cells;    macrophages;    IL-15;    trans-presentation;    CD70;   

DOI  :  10.1189/jlb.1209816

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

This study tested the hypothesis that individual myeloid subsets have a differential ability to maintain memory CD8 T cells via IL-15. Although DCs support IL-15-mediated homeostasis of memory CD8 T cells in vivo, whether various DC subsets and other myeloid cells similarly mediate homeostasis is unknown. Therefore, we studied the ability of different myeloid cells to maintain memory CD8 T cells in vitro. Using an in vitro cocoulture system that recapitulated known roles of DCs and IL-15 on memory CD8 T cells, all in vitro-derived or ex vivo-isolated DCs maintained CD8 T cells better than rIL-15 alone, and FLT-3L-DCs are the most efficient compared with GM-DCs, BM-derived macrophages, or freshly isolated DCs. Although FLT-3L-DCs were the least effective at inducing CD8 T cell proliferation, FLT-3L-DCs promoted better CD8 T cell survival and increased Bcl-2 and MCL-2 expression in CD8 T cells. T cell maintenance correlated only partially with DC expression of IL-15Rα and IL-15, suggesting that DCs provided additional support signals. Indeed, in the absence of IL-15 signals, CD70/CD27 further supported CD8 T cell maintenance. IFN-α enhanced CD70 expression by DCs, resulting in increased proliferation of CD8 T cells. Overall, this study supports our hypothesis by demonstrating that specific DC subtypes had a greater capacity to support memory CD8 T cell maintenance and did so through different mechanisms. Furthermore, this study shows that IL-15 trans-presentation can work in conjunction with other signals, such as CD70/CD27 interactions, to mediate CD8 T cell homeostasis efficiently.

【 授权许可】

Unknown