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Updated: Aug 12, 2026

Generation of Human CD40-activated B cells
13:27

Generation of Human CD40-activated B cells

Published on: October 17, 2009

CD40 ligand and CTLA-4 are reciprocally regulated in the Th1 cell proliferative response sustained by CD8(+)

Francesca Fallarino1, Ursula Grohmann, Carmine Vacca

  • 1Department of Experimental Medicine, University of Perugia, Perugia, Italy.

Journal of Immunology (Baltimore, Md. : 1950)
|July 23, 2002
PubMed

Insights

Murine dendritic cells (DCs) CD8(+) subsets impair Th1 T cell proliferation. CD40 activation of DCs or CTLA-4 neutralization in Th1 cells restores proliferation, suggesting reciprocal regulation.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Murine spleen dendritic cells (DCs) exhibit functional heterogeneity.
  • CD8(+) DCs may inadequately signal secondary CD4(+) T cells for sustained proliferation.
  • Differential DC subsets impact T cell responses.

Purpose of the Study:

  • To investigate the capacity of CD8(-) and CD8(+) DCs to stimulate Th1 and Th2 T cell clones.
  • To elucidate the role of CD40 signaling and CTLA-4 in DC-mediated T cell stimulation.

Main Methods:

  • Peptide-pulsed CD8(-) and CD8(+) DCs were used to stimulate Th1 and Th2 T cell clones.
  • CD40 triggering and CTLA-4 neutralization were employed during co-culture.
  • Expression of CD40 ligand and CTLA-4 on T cells was analyzed.

Main Results:

  • CD8(+) DCs selectively showed defective proliferation induction in Th1 cell clones.
  • CD40 triggering of CD8(+) DCs before antigen presentation restored Th1 proliferation.
  • In the absence of CD40 activation, Th1 cells showed low CD40 ligand and high CTLA-4 expression.
  • CTLA-4 neutralization enhanced Th1 proliferation and CD40 ligand expression.
  • CD40 activation on DCs downregulated CTLA-4 on Th1 cells.

Conclusions:

  • CD8(+) and CD8(-) DCs differentially affect antigen-primed T cell stimulation.
  • Reciprocal regulation between CD40 ligand and CTLA-4 expression occurs in Th1 cells interacting with CD8(+) DCs.
  • Modulating DC function via CD40 signaling can overcome T cell hyporesponsiveness.

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