title: CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation.
abstract: The clonal expansion of antigen-specific CD8+ T cells in response to microbial infections is essential for adaptive immunity. Although IL-2 has been considered to be primarily responsible for this process, quantitatively normal expansion occurs in the absence of IL-2 receptor signaling. Here, we show that ligating CD27 on CD8+ T cells that have been stimulated through the T cell receptor causes their expansion in the absence of IL-2 by mediating two distinct cellular processes: enhancing cell cycling and promoting cell survival by maintaining the expression of IL-7 receptor alpha. This pathway for clonal expansion of the CD8+ T cell is not associated with the development of a capacity either for production of IFN-gamma or for cytotoxic T lymphocyte function and, therefore, is uncoupled from differentiation. Furthermore, ligating CD27 increases the threshold concentration at which IL-2 induces IFN-gamma-producing capability by the CD8+ T cell, suggesting that CD27 signaling may suppress effector differentiation. Finally, CD8+ T cells that have been stimulated by the TCR/CD27 pathway maintain their capacity for subsequent expansion and effector differentiation in response to a viral challenge in vivo. Thus, the TCR/CD27 pathway enables the CD8+ T cell to replicate by a process of self-renewal, which may contribute to the continuous generation of new effector CD8+ T cells in persistent viral infections.
authors.affiliation: Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom.
authors.forename: James M
authors.initials: JM
authors.lastname: Carr
authors.forename: Marlene J
authors.initials: MJ
authors.lastname: Carrasco
authors.forename: James E D
authors.initials: JE
authors.lastname: Thaventhiran
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bambrough
authors.forename: Matthew
authors.initials: M
authors.lastname: Kraman
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Edwards
authors.forename: Aymen
authors.initials: A
authors.lastname: Al-Shamkhani
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Fearon
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D051379:Mice; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: D020395:Receptors, Interleukin-7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C415350:interleukin-7 receptor, alpha chain