Dimethyl sulfoxide (DMSO) exposure to human peripheral blood mononuclear cells (PBMCs) abolish T cell responses only in high concentrations and following coincubation for more than two hours
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- 作者：Henrik Kloverpris ; Anders Fomsgaard ; Am ; a H ; ley ; Jim Ackl ; Mark Sullivan ; Philip Goulder
- 关键词：DMSO ; T cell responses ; Polyfunctionality ; HIV ; Cell based immunotherapy
- 刊名：Journal of Immunological Methods
- 出版年：2010
- 出版时间：30 April 2010
- 年：2010
- 卷：356
- 期：1-2
- 页码：70-78
- 全文大小：988 K
文摘
Immunotherapies based on reinfusion of autologous cells incubated ex vivo with peptides reconstituted in toxic solvents, such as DMSO, are now performed on a routine basis. However, the toxic effects of the most common solvent used, DMSO, on T cell responses from human PBMCs, have not previously been evaluated in detail. Here, in preparation for a first-in-man human phase I vaccine trial comprising reinfusion of autologous HIV peptide-pulsed PBMCs, human PBMCs from healthy and HIV-infected donors were exposed in vitro to a range of DMSO concentrations, and for a range of time periods. Polychromatic flow cytometry was used to evaluate the influence of DMSO on functional T cell responses. We report that high concentrations of up to 10 % of DMSO for 1 hour do not affect the cell viability, the magnitude or the functional profile of CD4+ and CD8+ T cell responses, regardless of antigen specificity and HLA class I restriction. In contrast, > 2 % for > 2 hours compromises these responses. These data are relevant in the design of immunotherapies based on pulsing a large number of peptides onto antigen presenting cells prior to reinfusion.