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

Losana, Giuliana, Bovolenta, Chiara, Rigamonti, Laura, Borghi, Igor, Altare, Frederic, Jouanguy, Emmanuelle, Forni, Guido, Casanova, Jean-Laurent, Sherry, Barbara, Mengozzi, Manuela, Trinchieri, Giorgio, Poli, Guido, Gerosa, Franca and Novelli, Francesco (2002) IFN-gamma and IL-12 differentially regulate CC-chemokine secretion and CCR5 expression in human T lymphocytes. Journal of Leukocyte Biology, 72 (4). pp. 735-42. ISSN 0741-5400

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Interleukin (IL)-12, especially in the presence of neutralizing anti-IL-4 monoclonal antibodies, primed CD45RO(-) T clones for high CCL3/macrophage-inflammatory protein-1alpha (MIP-1alpha) and CCL4/MIP-1beta levels. In CD4(+) and CD8(+) clones from two patients deficient for IL-12Rbeta1 (IL-12Rbeta1(-/-)), production of CCL3/MIP-1alpha and CCL4/MIP-1beta was defective. CD4(+) clones from two patients deficient for interferon-gamma (IFN-gamma) R1 (IFN-gammaR1(-/-)) produced somewhat decreased CCL4/MIP-1beta 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-12Rbeta1(-/-) and IFN-gammaR1(-/-) 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-gamma increased CCR5 expression and decreased CC-chemokine secretion by CD4(+) clones from healthy and IL-12Rbeta1(-/-) individuals, suggesting an IFN-gamma-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-gamma receptor-deficient patients and dissect the role of IL-12 and IFN-gamma on inducing inflammatory chemokine secretion and down-regulating CCR5 expression in human T cells

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: Q Science > Q Science (General)
Depositing User: Manuela Mengozzi
Date Deposited: 14 Nov 2012 08:58
Last Modified: 05 Oct 2017 18:27
URI: http://sro.sussex.ac.uk/id/eprint/42336
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