CD40 ligand and IFN-γ synergistically restore IL-12 production in HIV-infected patients

Claire Chougnet, Elaine Thomas, Alan L. Landay, Harold A. Kessler, Susan Buchbinder, Susan Scheer, Gene M. Shearer

Research output: Contribution to journalArticlepeer-review


IL-12 production in HIV-infected (HIV+) individuals is severely impaired after stimulation by bacterial products or T cell-dependent stimuli. Because CD40-CD40 ligand (CD40L) interactions are the major mechanism involved in the T cell-dependent activation of antigen-presenting cells, we investigated whether this pathway was functional in HIV+ donors. CD40 expression was increased on freshly isolated monocytes from HIV+ individuals compared to HIV- donors. However, equivalent CD40 expression was obtained in the two groups after cytokine stimulation. Since CD40 expression was intact in HIV+ donors' cells, we determined whether IL-12 production could be restored by providing exogenous T cell-dependent stimuli, CD40L and IFN-γ, at the time of bacterial stimulation. IL-12 production was not altered by CD40L alone, was increased by IFN-γ, and was synergistically restored to normal values by IFN-γ + CD40L. This combination was more efficient for enhancing IL-12 production than granulocyte-macrophage colony-stimulating factor + CD40L or neutralizing anti-IL-10 antibody + CD40L. CD40L did not affect IL-10 production, whereas IFN-γ significantly decreased it. This study demonstrates that the defect in IL-12 production by leukocytes from HIV+ donors can be overcome in vitro if the interacting cells are provided with the right T cell-dependent co-stimuli.

Original languageEnglish (US)
Pages (from-to)646-656
Number of pages11
JournalEuropean Journal of Immunology
Issue number2
StatePublished - Feb 1998
Externally publishedYes


  • AIDS
  • Antigen-presenting cell
  • Co-stimulatory molecule
  • Cytokine
  • IL-10

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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