Regulatory T cell frequencies and phenotypes following anti-viral vaccination
Open Access
- 28 June 2017
- journal article
- clinical trial
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 12 (6), e0179942
- https://doi.org/10.1371/journal.pone.0179942
Abstract
Regulatory T cells (Treg) function in the prevention of excessive inflammation and maintenance of immunological homeostasis. However, these cells may also interfere with resolution of infections or with immune reactions following vaccination. Effects of Treg on vaccine responses are nowadays investigated, but the impact of vaccination on Treg homeostasis is still largely unknown. This may be a relevant safety aspect, since loss of tolerance through reduced Treg may trigger autoimmunity. In exploratory clinical trials, healthy adults were vaccinated with an influenza subunit vaccine plus or minus the adjuvant MF59®, an adjuvanted hepatitis B subunit vaccine or a live attenuated yellow fever vaccine. Frequencies and phenotypes of resting (rTreg) and activated (aTreg) subpopulations of circulating CD4+ Treg were determined and compared to placebo immunization. Vaccination with influenza vaccines did not result in significant changes in Treg frequencies and phenotypes. Vaccination with the hepatitis B vaccine led to slightly increased frequencies of both rTreg and aTreg subpopulations and a decrease in expression of functionality marker CD39 on aTreg. The live attenuated vaccine resulted in a decrease in rTreg frequency, and an increase in expression of activation marker CD25 on both subpopulations, possibly indicating a conversion from resting to migratory aTreg due to vaccine virus replication. To study the more local effects of vaccination on Treg in lymphoid organs, we immunized mice and analyzed the CD4+ Treg frequency and phenotype in draining lymph nodes and spleen. Vaccination resulted in a transient local decrease in Treg frequency in lymph nodes, followed by a systemic Treg increase in the spleen. Taken together, we showed that vaccination with vaccines with an already established safe profile have only minimal impact on frequencies and characteristics of Treg over time. These findings may serve as a bench-mark of inter-individual variation of Treg frequencies and phenotypes following vaccination.This publication has 45 references indexed in Scilit:
- Innate and adaptive immune responses in patients with pandemic influenza A(H1N1)pdm09Archiv für die gesamte Virusforschung, 2013
- Expression of CD39 on FoxP3+ T regulatory cells correlates with progression of HBV infectionBMC Immunology, 2012
- Foxp3+ regulatory T cells, immune stimulation and host defence against infectionImmunology, 2012
- Influenza A Virus Infection Results in a Robust, Antigen-Responsive, and Widely Disseminated Foxp3 + Regulatory T Cell ResponseJournal of Virology, 2012
- Dynamic variations in the peripheral blood lymphocyte subgroups of patients with 2009 pandemic H1N1 swine-origin influenza A virus infectionVirology Journal, 2011
- Expression of CD39 by Human Peripheral Blood CD4+CD25+ T Cells Denotes a Regulatory Memory PhenotypeAmerican Journal of Transplantation, 2010
- Regulatory T cells overturned: the effectors fight backImmunology, 2009
- Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppressionThe Journal of Experimental Medicine, 2007
- Activation/modulation of adaptive immunity emerges simultaneously after 17DD yellow fever first-time vaccination: is this the key to prevent severe adverse reactions following immunization?Clinical and Experimental Immunology, 2007
- Two subsets of memory T lymphocytes with distinct homing potentials and effector functionsNature, 1999