Environmental cues dictate the fate of individual CD8+ T cells responding to infection.
Many studies have examined pathways controlling effector T cell differentiation, but less is known about the fate of individual CD8+ T cells during infection. Here, we examine the antiviral and antibacterial responses of single CD8+ T cells from the polyclonal repertoire. The progeny of naive clonal CD8+ T cells displayed unique profiles of differentiation based on extrinsic pathogen-induced environmental cues, with some clones demonstrating extreme bias toward a single developmental pathway. Moreover, even within the same animal, a single naive CD8+ T cell exhibited distinct fates that were controlled by tissue-specific events. However, memory CD8+ T cells relied on intrinsic factors to control differentiation upon challenge. Our results demonstrate that stochastic and instructive events differentially contribute to shaping the primary and secondary CD8+ T cell response and provide insight into the underlying forces that drive effector differentiation and protective memory formation.
Center for Integrated Immunology and Vaccine Research, Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA. plumlee@uchc.edu
Courtney R
CR
Plumlee
Brian S
BS
Sheridan
Basak B
BB
Cicek
Leo
L
Lefrançois
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054243:Vesicular Stomatitis / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology