Generation of specific effector and memory T cells with gut- and secondary lymphoid tissue- homing potential by oral attenuated CVD 909 typhoid vaccine in humans

Abstract

Induction of effective memory T cells is likely to be critical to the level and duration of protection elicited by novel live oral typhoid vaccines. Using cells from volunteers who ingested Salmonella Typhi vaccine strain CVD 909, we characterized the induction of interferon (IFN)-γ-secreting central (TCM, CD45RO+ CD62L+) and effector (TEM, CD45RO+ CD62L-) memory T populations, and their gut-homing potential based on integrin α4/β7 expression. Both CD4+ TEM and TCM populations secreted IFN-γ. However, although CD4+ TEM expressed, or not, integrin α4/β7, CD4+ TCM cells were predominantly integrin α4/ β7+. In contrast, IFN-γ-secreting CD8+ cells were predominantly classical TEM and CD45RA+ TEM (TEMRA, CD45RO- CD62L-) subsets. However, although CD8+ TEM expressed, or not, integrin α4/ β7, CD8+ TEMRA were predominantly integrin α4/β7+. This is the first demonstration that oral immunization of humans with S. Typhi elicits diverse IFN-γ-secreting CD4+ and CD8+ TCM and TEM subsets able to migrate to the gut and other lymphoid tissues.