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

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

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

Eur J Immunol. 1998 Feb;28(2):646-56. Unique Identifier : AIDSLINE MED/98180370
Chougnet C; Thomas E; Landay AL; Kessler HA; Buchbinder S; Scheer S; Shearer GM; Experimental Immunology Branch, National Cancer Institute, Bethesda,; MD 20892, USA.

Abstract: 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-gamma, at the time of bacterial stimulation. IL-12 production was not altered by CD40L alone, was increased by IFN-gamma, and was synergistically restored to normal values by IFN-gamma + 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-gamma 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.

Keywords: *Antigens, CD40/METABOLISM *HIV Infections/IMMUNOLOGY *Interferon Type II/PHARMACOLOGY *Interleukin-12/BIOSYNTHESIS *Membrane Glycoproteins/PHYSIOLOGY
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