International Immunology, Vol 10, 1083-1091, Copyright © 1998 by Oxford University Press
C Johnson-Leger, J Christensen and GG Klaus
The ligand for CD40 (CD40L) is a protein which is expressed on CD4 T cells
following their activation: CD40-CD40L interactions are absolutely required
for the induction of T cell-dependent antibody responses, yet little is
known about the mechanisms whereby CD40L+ primary T cells activate naive B
cells, since the protein is only transiently expressed and is rapidly
down-regulated following T cell-B cell contact. We show here, using a
variety of assays, that co- stimulation of primary murine T cells via CD3
and CD28 stabilizes the expression of the CD40L protein. Firstly, T cells
stimulated in this manner express higher levels of CD40L when activated in
the presence of B cells, compared to CD3-activated T cells. Secondly, the
CD40L expressed on CD28-co-stimulated T cells is more resistant to B cell-
induced down-regulation. Finally, CD3/CD28-preactivated, rested T cells
re-express higher levels of CD40L more rapidly following re-stimulation via
CD3 than T cells preactivated via CD3 alone. CD3/CD28-preactivated T cells,
but not CD3-activated cells, are competent to induce DNA synthesis in naive
B cells, and this requires re-stimulation via CD3 and prolonged ligation of
CD40. These data therefore reinforce the concept that naive T cells need to
be activated initially by cognate interaction with B7-bearing
antigen-presenting cells (such as dendritic cells), before becoming
competent helper effector cells capable of driving B cells into
proliferation via a CD40-dependent pathway.
ARTICLES
CD28 co-stimulation stabilizes the expression of the CD40 ligand on T cells
Division of Cellular Immunology, National Institute for Medical Research, Mill Hill, London, UK.
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