title: Strength of stimulus and clonal competition impact the rate of memory CD8 T cell differentiation.
abstract: The developmental pathways of long-lived memory CD8 T cells and the lineage relationship between memory T cell subsets remain controversial. Although some studies indicate the two major memory T cell subsets, central memory T (T(CM)) and effector memory T (T(EM)), are related lineages, others suggest that these subsets arise and are maintained independently of one another. In this study, we have investigated this issue and examined the differentiation of memory CD8 T cell subsets by tracking the lineage relationships of both endogenous and TCR transgenic CD8 T cell responses after acute infection. Our data indicate that TCR transgenic as well as nontransgenic T(EM) differentiate into T(CM) in the absence of Ag. Moreover, the rate of memory CD8 T cell differentiation from T(EM) into the self-renewing and long-lived pool of T(CM) is influenced by signals received during priming, including Ag levels, clonal competition, and/or the duration of infection. Although some T(EM) appear to not progress to T(CM), the vast majority of T(CM) are derived from T(EM). Thus, long-lasting, Ag-independent CD8 T cell memory results from progressive differentiation of memory CD8 T cells, and the rate of memory T cell differentiation is governed by events occurring early during T cell priming.
authors.affiliation: Department of Microbiology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Surojit
authors.initials: S
authors.lastname: Sarkar
authors.forename: Volker
authors.initials: V
authors.lastname: Teichgräber
authors.forename: Vandana
authors.initials: V
authors.lastname: Kalia
authors.forename: Antonio
authors.initials: A
authors.lastname: Polley
authors.forename: David
authors.initials: D
authors.lastname: Masopust
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Harrington
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
mesh_terms: D000208:Acute Disease; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D011948:Receptors, Antigen, T-Cell