title: Preformed CD40 ligand exists in secretory lysosomes in effector and memory CD4+ T cells and is quickly expressed on the cell surface in an antigen-specific manner.
abstract: CD40 ligand (CD40L) is an essential effector cytokine for macrophage activation, dendritic cell licensing, and T-cell-dependent antibody responses. Although CD40L is known to be made de novo following antigen recognition, several reports have described surface mobilization of preformed, intracellular CD40L in certain CD4(+) effector T cells. Here we show that rapid surface expression of preformed CD40L following antigen recognition is a general property of both effector and memory CD4(+) T cells, including in vitro and in vivo activated T-cell-receptor transgenic T cells, memory phenotype CD4(+) T cells from pathogen-free naive mice, and polyclonal virus-specific effector and memory T cells. Intracellular CD40L is stored in secretory lysosomes, and colocalizes more strongly with Fas ligand than with CTLA-4, two other molecules that are delivered to the cell surface following antigen recognition. Stimulated surface expression of preformed CD40L is found in memory CD4(+) T cells from CD40-deficient mice, indicating that it does not depend on CD40-induced internalization for delivery to the secretory compartment. We suggest that delivery of preformed CD40L to antigen-presenting cells (APCs) could enable antigen-specific activation of APCs in transient interactions that are too brief to permit de novo synthesis of CD40L.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Koguchi
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Thauland
authors.forename: Mark K
authors.initials: MK
authors.lastname: Slifka
authors.forename: David C
authors.initials: DC
authors.lastname: Parker
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D060908:CTLA-4 Antigen; D002465:Cell Movement; D007156:Immunologic Memory / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D023201:CD40 Ligand