High-intensity interval training in allogeneic adoptive T-cell immunotherapy - a big HIT?
JOURNAL OF TRANSLATIONAL MEDICINE
Authors: Heinemann, Nele Carolin; Tischer-Zimmermann, Sabine; Wittke, Torge Christian; Eigendorf, Julian; Kerling, Arno; Framke, Theodor; Melk, Anette; Heuft, Hans-Gert; Blasczyk, Rainer; Maecker-Kolhoff, Britta; Eiz-Vesper, Britta
Abstract
Background Adoptive transfer of virus-specific T cells (VSTs) represents a prophylactic and curative approach for opportunistic viral infections and reactivations after transplantation. However, inadequate frequencies of circulating memory VSTs in the T-cell donor's peripheral blood often result in insufficient enrichment efficiency and purity of the final T-cell product, limiting the effectiveness of this approach. Methods This pilot study was designed as a cross-over trial and compared the effect of a single bout (30 min) of high-intensity interval training (HIT) with that of 30 min of continuous exercise (CONT) on the frequency and function of circulating donor VSTs. To this end, we used established immunoassays to examine the donors' cellular immune status, in particular, with respect to the frequency and specific characteristics of VSTs restricted against Cytomegalovirus (CMV)-, Epstein-Barr-Virus (EBV)- and Adenovirus (AdV)-derived antigens. T-cell function, phenotype, activation and proliferation were examined at different time points before and after exercise to identify the most suitable time for T-cell donation. The clinical applicability was determined by small-scale T-cell enrichment using interferon- (IFN-) gamma cytokine secretion assay and virus-derived overlapping peptide pools. Results HIT proved to be the most effective exercise program with up to fivefold higher VST response. In general, donors with a moderate fitness level had higher starting and post-exercise frequencies of VSTs than highly fit donors, who showed significantly lower post-exercise increases in VST frequencies. Both exercise programs boosted the number of VSTs against less immunodominant antigens, specifically CMV (IE-1), EBV (EBNA-1) and AdV (Hexon, Penton), compared to VSTs against immunodominant antigens with higher memory T-cell frequencies. Conclusion This study demonstrates that exercise before T-cell donation has a beneficial effect on the donor's cellular immunity with respect to the proportion of circulating functionally active VSTs. We conclude that a single bout of HIT exercise 24 h before T-cell donation can significantly improve manufacturing of clinically applicable VSTs. This simple and economical adjuvant treatment proved to be especially efficient in enhancing virus-specific memory T cells with low precursor frequencies.
On Rigid Minimal Spaces
JOURNAL OF DYNAMICS AND DIFFERENTIAL EQUATIONS
Authors: Boronski, Jan P.; Cinc, Jernej; Forys-Krawiec, Magdalena
Abstract
A compact space X is said to be minimal if there exists a map f : X -> X such that the forward orbit of any point is dense in X. We consider rigid minimal spaces, motivated by recent results of Downarowicz, Snoha and Tywoniuk (J Dyn Differ Equ, 29:243-257, 2017) on spaces with cyclic group of homeomorphisms generated by a minimal homeomorphism, and results of the first author, Clark and Oprocha (Adv Math, 335:261-275, 2018) on spaces in which the square of every homeomorphism is a power of the same minimal homeomorphism. We show that the two classes do not coincide, which gives rise to a new class of spaces that admit minimal homeomorphisms, but no minimal maps. We modify the latter class of examples to show for the first time existence of minimal spaces with degenerate homeomorphism groups. Finally, we give a method of constructing decomposable compact and connected spaces with cyclic group of homeomorphisms, generated by a minimal homeomorphism, answering a question in Downarowicz et al.