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

Yoshinobu Koguchi, Timothy J. Thauland, Mark Slifka, David Parker

Research output: Contribution to journalArticle

51 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2520-2527
Number of pages8
JournalBlood
Volume110
Issue number7
DOIs
StatePublished - Oct 1 2007

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CD40 Ligand
T-cells
Surface Antigens
Lysosomes
T-Lymphocytes
Antigens
Data storage equipment
Antigen-Presenting Cells
Chemical activation
Fas Ligand Protein
Macrophage Activation
Macrophages
Pathogens
Licensure
T-Cell Antigen Receptor
Viruses
Dendritic Cells
Antibody Formation
Cytokines
Phenotype

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Koguchi, Yoshinobu; Thauland, Timothy J.; Slifka, Mark; Parker, David.

In: Blood, Vol. 110, No. 7, 01.10.2007, p. 2520-2527.

Research output: Contribution to journalArticle

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