Name
Rotavirus-specific intestinal resident memory T cells induced by oral vaccination in early-life mice play a role in disease protection
Presenter
Catherine Montenegro Chávez, Pontificia Universidad Javeriana
Co-Author(s)
Federico Perdomo Celis (Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia)
Manuel Antonio Franco Cortes (Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia)
Abstract Category
Pathogenesis and Immunity
Abstract
It is unknown whether intestinal resident memory T cells (Trmi) are induced and play a role in protecting against rotavirus (RV) infection in early life, as well as the role of TGFβ and the α4β7 integrin in the differentiation of this population.
Five- to six-day-old C57BL/6 mice were orally vaccinated with the heterologous rhesus RV, and then challenged with murine EC RV. The frequency and phenotype of total and RV-specific Trmi were characterized by intravascular staining (anti-CD45.2 antibody), and MHC class I and II tetramers. To evaluate the protection conferred by RV-specific Trmi, NAD+ was administered to deplete this population in the intraepithelial compartment. In addition, we evaluated the impact of an anti-TGFβ and anti-α4β7 antibody in the frequency and phenotype of total and RV-specific Trmi.
RV-specific Trmi were induced in early-life mice, and they were mostly CD45.2- CD8+ CD69+ CD103+ P2X7R+ in the intraepithelial compartment, or CD45.2- CD4+ CD69+ CD103- P2X7R+ in lamina propria. Upon NAD+ treatment, an increase in viral excretion was observed, suggestive of decreased disease protection. Blockade of α4β7 reduced the numbers of T cells with a CD45.2- CD4+ CD69+ CD103- P2X7R+ phenotype in lamina propria, while TGFβ blockade caused the decrease of intraepithelial T cells with a CD45.2- CD8+ CD103+ phenotype.
This study is the first to report early-life Trmi in RV infection, indicating their potential role in mediating disease protection and informing RV vaccine development.
Five- to six-day-old C57BL/6 mice were orally vaccinated with the heterologous rhesus RV, and then challenged with murine EC RV. The frequency and phenotype of total and RV-specific Trmi were characterized by intravascular staining (anti-CD45.2 antibody), and MHC class I and II tetramers. To evaluate the protection conferred by RV-specific Trmi, NAD+ was administered to deplete this population in the intraepithelial compartment. In addition, we evaluated the impact of an anti-TGFβ and anti-α4β7 antibody in the frequency and phenotype of total and RV-specific Trmi.
RV-specific Trmi were induced in early-life mice, and they were mostly CD45.2- CD8+ CD69+ CD103+ P2X7R+ in the intraepithelial compartment, or CD45.2- CD4+ CD69+ CD103- P2X7R+ in lamina propria. Upon NAD+ treatment, an increase in viral excretion was observed, suggestive of decreased disease protection. Blockade of α4β7 reduced the numbers of T cells with a CD45.2- CD4+ CD69+ CD103- P2X7R+ phenotype in lamina propria, while TGFβ blockade caused the decrease of intraepithelial T cells with a CD45.2- CD8+ CD103+ phenotype.
This study is the first to report early-life Trmi in RV infection, indicating their potential role in mediating disease protection and informing RV vaccine development.