Using reporter mouse models to track CD4 T cell differentiation and fate based on IL-2 expression (P1199)

Abstract

Abstract CD4 T cells respond to in vivo activation stimuli, in part, by rapidly producing the homeostatic cytokine IL-2. It is thought that this acute production of IL-2 is necessary for full activation and fate determination of both the conventional CD4 T cells themselves, as well as other components of the adaptive (Tregs/CD8/B cells) and innate immune responses (NK/NKT/DC) to infection. Within a population of responding CD4 T cells, only a percentage of cells will secrete IL-2. Though much is known regarding regulation of IL-2 production by CD4 T cells and the downstream consequences of autocrine and paracrine signaling, little is known about the quantity, quality, or fate of CD4 T cells that produce IL-2. Using L. monocytogenes engineered to express foreign MHCII peptides and peptide-loaded MHCII tetramers, we are able to track and assess the fate of endogenous, antigen-specific CD4 T cells in infected mice. Combining this methodology with novel transgenic IL-2 reporter mouse models, we are able to address questions regarding fate by isolating, depleting, and/or adoptively transferring live, antigen-specific CD4 T cells to secondary hosts based on acute expression of IL-2. Preliminary data suggests IL-2-‘competent’ and -‘incompetent’ cells differ in their ability to traffic to peripheral tissues following an acute, systemic infection, resulting in a potential functional, as well as proliferative and survival advantage for competent cells over those incompetent for IL-2 expression.