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3. Regulatory T cell frequencies and phenotypes following anti-viral vaccination

Author

de Wolf, A Charlotte M T, van Aalst, Susan, Ludwig, Irene S, Bodinham, Caroline L, Lewis, David J, van der Zee, Ruurd, van Eden, Willem, Broere, Femke, de Wolf, A Charlotte M T, van Aalst, Susan, Ludwig, Irene S, Bodinham, Caroline L, Lewis, David J, van der Zee, Ruurd, van Eden, Willem, and Broere, Femke

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 frequenc

Published
2017

4. Regulatory T cell frequencies and phenotypes following anti-viral vaccination

Author

dI&I RA-I&I I&I, de Wolf, A Charlotte M T, van Aalst, Susan, Ludwig, Irene S, Bodinham, Caroline L, Lewis, David J, van der Zee, Ruurd, van Eden, Willem, Broere, Femke, dI&I RA-I&I I&I, de Wolf, A Charlotte M T, van Aalst, Susan, Ludwig, Irene S, Bodinham, Caroline L, Lewis, David J, van der Zee, Ruurd, van Eden, Willem, and Broere, Femke

Published
2017

8. Bystander activation of irrelevant CD4+ T cells following antigen-specific vaccination occurs in the presence and absence of adjuvant.

Author

van Aalst, Susan, Ludwig, Irene S., van der Zee, Ruurd, van Eden, Willem, and Broere, Femke

Subjects
*AUTOIMMUNE disease prevention, *IMMUNOLOGICAL adjuvants, *VACCINATION, *CD4 antigen, *T cells, *QUALITY of life, *DISEASE prevalence, *ETIOLOGY of diseases
Abstract

Autoimmune and other chronic inflammatory diseases (AID) are prevalent diseases which can severely impact the quality of life of those that suffer from the disease. In most cases, the etiology of these conditions have remained unclear. Immune responses that take place e.g. during natural infection or after vaccination are often linked with the development or exacerbation of AID. It is highly debated if vaccines induce or aggravate AID and in particular adjuvants are mentioned as potential cause. Since vaccines are given on a large scale to healthy individuals but also to elderly and immunocompromised individuals, more research is warranted. Non-specific induction of naïve or memory autoreactive T cells via bystander activation is one of the proposed mechanisms of how vaccination might be involved in AID. During bystander activation, T cells unrelated to the antigen presented can be activated without (strong) T cell receptor (TCR) ligation, but via signals derived from the ongoing response directed against the vaccine-antigen or adjuvant at hand. In this study we have set up a TCR transgenic T cell transfer mouse model by which we were able to measure local bystander activation of transferred and labeled CD4+ T cells. Intramuscular injection with the highly immunogenic Complete Freund’s Adjuvant (CFA) led to local in vivo proliferation and activation of intravenously transferred CD4+ T cells in the iliac lymph node. This local bystander activation was also observed after CFA prime and Incomplete Freund’s Adjuvant (IFA) boost injection. Furthermore, we showed that an antigen specific response is sufficient for the induction of a bystander activation response and the general, immune stimulating effect of CFA or IFA does not appear to increase this effect. In other words, no evidence was obtained that adjuvation of antigen specific responses is essential for bystander activation. [ABSTRACT FROM AUTHOR]

Published
2017
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