title: Derivation and fluidity of acutely induced dysfunctional CD8+ T cells.
abstract: Dysfunctional CD8(+) T (T(CD8(+))) cells lacking cytokine production have been identified in many viral infections, but their genesis is not well understood. Established results indicate that such cells could be either high avidity that enter a refractory state due to overstimulation or low avidity that are only partially stimulated. Using an acute, resolving infection model that results in rapid production of dysfunctional cells, we show that this IL2 unresponsive phenotype emerges from the low end of the avidity spectrum and is characterized by broad TCR usage and a reduced proliferation rate. Furthermore, the dysfunctional population is extremely fluid, being sustained by high Ag dose but virtually eliminated following low dose boosting. Together, these results suggest that persistence of dysfunctional cells generated in this manner depends upon continual exposure to high Ag levels and that such cells may ultimately predominate if functional cells become exhausted.
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Plesa
authors.forename: Adam E
authors.initials: AE
authors.lastname: Snook
authors.forename: Scott A
authors.initials: SA
authors.lastname: Waldman
authors.forename: Laurence C
authors.initials: LC
authors.lastname: Eisenlohr
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D000939:Epitopes; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell