Investigating The Possible Role Of Regulatory T Cells In Suppressing DTwP And Measles-Vaccine Induced Responses In 9 Month-Old Gambian Infants

Ndure, Yai Jorjoh (2018). Investigating The Possible Role Of Regulatory T Cells In Suppressing DTwP And Measles-Vaccine Induced Responses In 9 Month-Old Gambian Infants. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000d93d

Abstract

The majority of deaths in children under five are attributed to infections, with neonates and young infants being the most susceptible. The immune system of the newborn is adapted to protect the fetus from infections and avoid harmful inflammation, characterized by limited Th1 immunity and skewed towards Th2 and immunoregulatory responses. This results in high susceptibility to infections and impaired responses to vaccines. Regulatory T cells (Tregs) control pro-inflammatory responses and are therefore important in maintaining a fine balance of immune responses during infections. Tregs are high and functional in neonates, but their precise role in controlling vaccine immunogenicity is not known.

I hypothesised that circulating Tregs at vaccination can limit subsequent vaccine-induced cellular and humoral responses, and that functional Tregs are induced by vaccination in infants. The work in this thesis involves the characterization of Tregs before and after measles and Diphtheria, Tetanus and whole cell pertussis combined (DTwP) vaccination, and association with functional readouts, vaccine-specific humoral and cellular responses. I found that CD4+FOXP3+CD127lo Tregs significantly declined overtime, with this subset and the CD4+CD25hiFOXP3+ Treg subsets inversely correlating with the measles antibodies following vaccination. This supports a functional role for Tregs in controlling the humoral response to measles but not for DTwP vaccination. We also observe an induction of CD4+IL-10+ T cells following measles vaccination. Further evaluation of these cells showed that they were mainly IL-4- and IFN-γ-, excluding the possibility that these may be Th1 or Th2 cells, and suggesting that these may be Tr1 cells induced as part of a homeostatic control mechanism following MV. Further evaluation of the role of Tregs in vaccine immunogenicity in infants is warranted.

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