IFN-γ IL-12 differentially regulate CC-chemokine secretion and CCR5 expression in human T lymphocytes

Giuliana Losana, Chiara Bovolenta, Laura Rigamonti, Igor Borghi, Frederic Altare, Emmanuelle Jouanguy, Guido Forni, Jean Laurent Casanova, Barbara Sherry, Manuela Mengozzi, Giorgio Trinchieri, Guido Poli, Franca Gerosa, Francesco Novelli

Research output: Contribution to journalArticlepeer-review


Interleukin (IL)-12, especially in the presence of neutralizing anti-IL-4 monoclonal antibodies, primed CD45RO- T clones for high CCL3/macrophage-inflammatory protein-1α (MIP-1α) and CCL4/MIP-1β levels. In CD4+ and CD8+ clones from two patients deficient for IL-12Rβ1 (IL-12Rβ1-/-), production of CCL3/MIP-1α and CCL4/MIP-1β was defective. CD4+ clones from two patients deficient for interferon-γ (IFN-γ) R1 (IFN-γR1-/-) produced somewhat decreased CCL4/MIP-1β levels. IL-12 failed to prime CD4+ or CD8+ healthy clones for high CCL5/regulated on activation, normal T expressed and secreted (RANTES) production, although its secretion was impaired in CD4+ clones from IL-12Rβ1-/- and IFN-γR1-/- patients. CCR5 surface expression was up-regulated in resting peripheral blood mononuclear cells and CD4+ clones from both kinds of patients, rendering them more susceptible to CCR5-dependent (R5) HIV-1 infection. Neutralization of IFN-γ increased CCR5 expression and decreased CC-chemokine secretion by CD4+ clones from healthy and IL-12Rβ1-/- individuals, suggesting an IFN-γ-dependent control of CCR5 expression. These data provide the first documented analysis of chemokine secretion and chemokine receptor expression on T cells from IL-12 and IFN-γ receptor-deficient patients and dissect the role of IL-12 and IFN-γ on inducing inflammatory chemokine secretion and down-regulating CCR5 expression in human T cells.

Original languageEnglish
Pages (from-to)735-742
Number of pages8
JournalJournal of Leukocyte Biology
Issue number4
Publication statusPublished - Oct 1 2002


  • AIDS
  • Chemokine receptor
  • Cytokine receptors

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'IFN-γ IL-12 differentially regulate CC-chemokine secretion and CCR5 expression in human T lymphocytes'. Together they form a unique fingerprint.

Cite this