Naïve Ag-specific CD8 T cell precursors respond to pathogen-derived antigens, undergo vigorous clonal expansion, acquire effector functions and develop into memory CD8 T cell populations (Figure 1). Memory CD8 T cells can protect from re-infection with the same or related intracellular pathogens, and vaccine-evoked CD8 T cells hold great potential for the prevention of infectious diseases. New experimental approaches and models to dissect immune responses in health and disease led to increased understanding of the cellular and molecular mechanisms that control the abundance, quality, and maintenance of the memory CD8 T cell pool.
Figure 1. – Population dynamics of primary and multiple stimulated CD8 T cell responses – A Model. After antigen (Ag)-encounter naïve and memory CD8 T cells (primary, secondary, tertiary) undergo proliferative expansion. The magnitude of expansion, duration of contraction, and ability to generate long-lived progeny (‘memory generation potential’) of naïve and /or memory CD8 T cells is dependent on the Ag stimulation history.
Our main research goals are to:
1) Establish relevant experimental models to study antigen-experienced CD8 T cells in vivo;
2) Determine the factors that influence generation, maintenance and function of memory CD8 T cells;
3) Characterize CD8 T cells responding to multiple rounds of antigenic stimulations;
4) Investigate the alterations in T cell-mediated immunity that occur after sepsis; and
5) Define sepsis-induced state of immunoparalysis and explore treatments to restore immunity in sepsis survivors.