title: Expansion of activated human naïve T-cells precedes effector function.
abstract: Naïve T-cells divide and mature, both functionally and phenotypically, upon stimulation through the T-cell receptor. Although much is known about the overall changes that occur in naïve cells upon TCR stimulation, and the different memory/effector populations that arise following stimulation, the relationship between cell division and functional and phenotypical changes that occur after activation is poorly understood. Here, we examine the early stages of human naïve and antigen-experienced T-cell activation, and the relationship between cell division and acquisition of effector function during the transition from resting antigen-experienced or naïve T-cells into effector cells. Stimulated naïve T-cells proliferate prior to acquisition of effector function, as measured by cytokine production and expression of effector-associated cell surface molecules. Additionally, we show that interlukin-7 (IL-7) can drive proliferation of naïve T-cells without TCR:MHC peptide interactions. IL-7 alone does not, however, drive the proliferation of antigen-experienced T-cells. Memory T-cells will divide in response to exogenous IL-7 but only in the presence of naïve T-cells and IL-2. This study contributes to the current understanding of the mechanistic differences between naïve and memory T-cell responses by defining the functional and phenotypic changes that occur to T-cells after stimulation.
authors.affiliation: Vaccine Research Center, NIAID and Department of Experimental Transplantation and Immunology, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: D C
authors.initials: DC
authors.lastname: Douek
authors.forename: D R
authors.initials: DR
authors.lastname: Ambrozak
authors.forename: M
authors.initials: M
authors.lastname: Chatterji
authors.forename: M R
authors.initials: MR
authors.lastname: Betts
authors.forename: L S
authors.initials: LS
authors.lastname: Davis
authors.forename: R A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D000941:Antigens / Q000032:analysis / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000941:Antigens; D007376:Interleukin-2; D015851:Interleukin-7