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

Abstract

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.

Adjuvant Effects of a CC Chemokine for Enhancing the Efficacy of an Inactivated Streptococcus agalactiae Vaccine in Nile Tilapia (Oreochromis niloticus)

“…Additionally, immune-related genes such as TNF alpha-induced protein 6, B-cell scaffold protein, and major histocompatibility complex class I exhibited notable upregulation, further indicating the enhancement of immune activation by the inclusion of On -CC1 as an effective adjuvant in the formulation. Interestingly, upregulated expression of various interleukins and chemokines was also observed, indicating the involvement of inflammatory and chemotactic pathways in the immune response elicited by the WC+CC vaccine [ 43 , 44 , 45 , 46 , 47 , 48 , 49 ], supporting findings from previous gene expression analysis experiments using qRT–PCR.…”

“…While no significant differences were detected between the WC and WC+CC vaccine groups in the kidney, more significant differences were detected at 168 hpv in the spleen, with the WC+CC group exhibiting higher upregulation of TNF-α expression than the WC group. Similarly, IFN-α was highly upregulated in all vaccinated groups compared to the unvaccinated group, with significant differences between the WC and WC+CC groups observed in the head kidney at 6 hpv and in the spleen at 24 hpv, further highlighting the enhanced immune activation conferred by the WC+CC vaccine [ 45 , 46 ]. Moreover, IL-8(1) and ( CXC1 ) IL-1β transcriptional levels were markedly increased in both the WC and WC+CC vaccine groups compared to those in the control unvaccinated group at multiple time points, with significant differences between the WC and WC+CC vaccinated groups observed at specific time points.…”