Protective effector memory CD4+ T cells are generated from an early effector memory precursor (MPF6P.739)

Abstract

Abstract Effector memory CD4+ T cells (Tem) are the predominant memory subset in chronic infections such as malaria and tuberculosis. Tem respond quickly by making effector cytokines. Therefore, understanding their mechanism of generation and the role of persistent antigen is essential for vaccination strategies. The current paradigm of Tem generation is that they develop progressively from mature effector T cells in the contraction phase, however this remains to be established. In order to identify a precursor of Tem we identified three effector subsets with an Early CD127-CD62Lhi CD4+ memory precursor effector T cell (MPEC) population, and short-lived CD62Llo Teff (SLEC). In adoptive transfer experiments, we show the potential of Early Teff to diverge into either terminal Teff or memory cells depending on the environment, while mature Teff lose their memory potential, in contrast to the progressive differentiation model. Furthermore, we demonstrate that resting central memory T cells can become Tem in the absence of further stimulation. All three effector subsets protect immunocompromised animals, however, only Late Effector memory (TemL) improves both infection and pathology. Based on our data we propose an early decision point for generation of protective effector memory T cells, suggesting that memory development occurs in the early phase of activation. This work also suggests that TemL represent a correlate of immunity in chronic infection and can improve vaccine design studies.