Airway hyperresponsiveness was tested by provocation with increasing doses of MCh aerosol and according to ethics approval provocation was terminated once an animal had reached the ED200 or above. Dried aerosols were generated by a computer-controlled aerosol generator system (Bronchy III+feedback dose control system, Fraunhofer Institute, Hannover,

Germany). All values are expressed as mean+SEM. Statistical analysis was performed using one-way ANOVA (Bonferroni post hoc test) or Mann–Whitney U-test using PRISM 4 (GraphPad, La Jolla, CA, USA). A p-value <0.05 was considered as statistically significant. The authors thank Karin Westermann and Marion Hitzigrath for their excellent technical assistance. We acknowledge the excellent technical assistance of the members of the Hannover Medical School Core Facility for Cell Sorting and would like to thank

Shahzad N. Syed AZD2014 for providing the Fc RIV-specific RT-PCR primers. We especially thank Heinz-Gerd Hoymann for the lung function measurements. We thank Rachel Thomas for carefully editing and improving the manuscript. This work was supported by Deutsche Forschungsgemeinschaft SFB 587 (B5), a grant of StrucMed to M.M., a grant of GK1441 to J.K.K., and partially by a grant from the Excellence Cluster “From Regenerative Biology to Reconstructive LY2835219 concentration Therapy” (German Research Foundation) to G.M.N.B. Conflict of interest: The authors declare no financial or commercial conflict on interest.

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“A critical component of vaccine design is to generate and maintain antigen-specific memory lymphocytes of sufficient quantity and quality to give the host life-long protection against re-infection. Therefore, it is important to understand how memory T cells acquire the ability for self-renewal while retaining a potential for heightened recall of effector functions. During acute viral infection or following vaccination, antigen-specific T cells undergo extensive phenotypic and functional changes during differentiation to the effector and memory phases of the immune response. The changes in cell phenotype that accompany memory T-cell differentiation are predominantly very mediated through acquired transcriptional regulatory mechanisms, in part achieved through epigenetic modifications of DNA and histones. Here we review our current understanding of epigenetic mechanisms regulating the off-on-off expression of CD8 and CD4 T-cell effector molecules at naive, effector and memory stages of differentiation, respectively, and how covalent modifications to the genome may serve as a mechanism to preserve ‘poised’ transcriptional states in homeostatically dividing memory cells. We discuss the potential of such mechanisms to control genes that undergo on-off-on patterns of expression including homing and pro-survival genes, and the implications on the development of effector-memory and central-memory T-cell differentiation.