期刊
PLOS ONE
卷 7, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0030229
关键词
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资金
- Madeleine Franchi Ovarian Research Fund
- Dunkin Donuts Rising Stars Awards
- Cancer Research Institute
- NIH [K22 CA129240, R01 CA148673]
- American Society of Hematology
- Grants-in-Aid for Scientific Research [21591217] Funding Source: KAKEN
Background: Using in vivo mouse models, the mechanisms of CD4(+) T cell help have been intensively investigated. However, a mechanistic analysis of human CD4(+) T cell help is largely lacking. Our goal was to elucidate the mechanisms of human CD4(+) T cell help of CD8(+) T cell proliferation using a novel in vitro model. Methods/Principal Findings: We developed a genetically engineered novel human cell-based artificial APC, aAPC/mOKT3, which expresses a membranous form of the anti-CD3 monoclonal antibody OKT3 as well as other immune accessory molecules. Without requiring the addition of allogeneic feeder cells, aAPC/mOKT3 enabled the expansion of both peripheral and tumor-infiltrating T cells, regardless of HLA-restriction. Stimulation with aAPC/mOKT3 did not expand Foxp3(+) regulatory T cells, and expanded tumor infiltrating lymphocytes predominantly secreted Th1-type cytokines, interferonthis aAPC-based system, the presence of autologous CD4(+) T cells was associated with significantly improved CD8(+) T cell expansion in vitro. The CD4(+) T cell derived cytokines IL-2 and IL-21 were necessary but not sufficient for this effect. However, CD4(+) T cell help of CD8(+) T cell proliferation was partially recapitulated by both adding IL-2/IL-21 and by upregulation of IL21 receptor on CD8(+) T cells. Conclusions: We have developed an in vitro model that advances our understanding of the immunobiology of human CD4(+) T cell help of CD8(+) T cells. Our data suggests that human CD4(+) T cell help can be leveraged to expand CD8(+) T cells in vitro.
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