Human neutrophil-expressed CD28 interacts with macrophage B7 to induce phosphatidylinositol 3-kinase-dependent IFN-γ secretion and restriction of Leishmania growth

K. Venuprasad, Pinaki P. Banerjee, Subhasis Chattopadhyay, Satyan Sharma, Subrata Pal, P. B. Parab, Debashis Mitra, Bhaskar Saha

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

We previously showed that CD28 is expressed on human peripheral blood neutrophils and plays an important role in CXCR-1 expression and IL-8-induced neutrophil migration. In this work we demonstrate that Leishmania major infection of macrophages results in parasite dose-dependent IL-8 secretion in vitro and in IL-8-directed neutrophil migration, as blocked by both anti-IL-8 and anti-IL-8R Abs, toward the L. major-infected macrophages. In the neutrophil-macrophage cocultures, both CTLA4-Ig, a fusion protein that blocks CD28-CD80/CD86 interaction, and a neutralizing anti-IFN-γ Ab inhibit the anti-leishmanial function of neutrophils, suggesting that the neutrophil-macrophage interaction via CD28-CD80/CD86 plays an important role in the IFN-γ-dependent restriction of the parasite growth. Cross-linking of neutrophil-expressed CD28 by monoclonal anti-CD28 Ab or B7.1-Ig or B7.2-Ig results in phosphatidylinositol 3-kinase association with CD28 and in wortmannin-sensitive but cyclosporin A-resistant induction and secretion of IFN-γ. Whereas the neutrophils secrete IFN-γ with CD28 signal alone, the T cells do not secrete the cytokine in detectable amounts with the same signal. Thus, neutrophil-expressed CD28 modulates not only the granulocyte migration but also induction and secretion of IFN-γ at the site of infection where it migrates from the circulation.

Original languageEnglish (US)
Pages (from-to)920-928
Number of pages9
JournalJournal of Immunology
Volume169
Issue number2
DOIs
StatePublished - Jul 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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