Ex Vivo Expansion of Human CD8+ T Cells Using Autologous CD4+ T Cell Help

Ex Vivo Expansion of Human CD8+ T Cells Using Autologous CD4+ T Cell Help

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Ex Vivo Expansion of Human CD8+ T Cells Using Autologous CD4+ T Cell Help

dc.contributor.author	Butler, Marcus O.
dc.contributor.author	Imataki, Osamu
dc.contributor.author	Yamashita, Yoshihiro
dc.contributor.author	Tanaka, Makito
dc.contributor.author	Ansén, Sascha
dc.contributor.author	Berezovskaya, Alla
dc.contributor.author	Metzler, Genita
dc.contributor.author	Milstein, Matthew I.
dc.contributor.author	Mooney, Mary M.
dc.contributor.author	Mano, Hiroyuki
dc.contributor.author	Murray, Andrew P.
dc.contributor.author	Nadler, Lee Marshall
dc.contributor.author	Hirano, Naoto
dc.date.accessioned	2012-05-09T00:42:04Z
dc.date.issued	2012
dc.identifier.citation	Butler, Marcus O., Osamu Imataki, Yoshihiro Yamashita, Makito Tanaka, Sascha Ansén, Alla Berezovskaya, Genita Metzler, Matthew I. Milstein, Mary M. Mooney, Andrew P. Murray, Hiroyuki Mano, Lee M. Nadler, and Naoto Hirano. 2012. Ex vivo expansion of human cd8+ t cells using autologous cd4+ t cell help. PLoS ONE 7(1): e30229.	en_US
dc.identifier.issn	1932-6203	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:8704117
dc.description.abstract	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, interferon-γ and IL-2. In this 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 IL-21 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.	en_US
dc.language.iso	en_US	en_US
dc.publisher	Public Library of Science	en_US
dc.relation.isversionof	doi:10.1371/journal.pone.0030229	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257268/pdf/	en_US
dash.license	LAA
dc.title	Ex Vivo Expansion of Human CD8+ T Cells Using Autologous CD4+ T Cell Help	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	PLoS ONE	en_US
dash.depositing.author	Nadler, Lee Marshall
dc.date.available	2012-05-09T00:42:04Z