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

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.