Differential regulation of Th1 responses and CD154 expression in human CD4+ T cells by IFN-α

Abstract

SUMMARYLike interleukin (IL)-12, interferon (IFN)-a has been shown to play an important role in inducing human Th1 responses. Recent studies have shown that human Th1 responses driven by IL-12 are associated with enhanced expression of CD154. The present study examined the effects of IFN-a on CD154 expression in human CD4 + T cells, with special attention to the relationship with Th1 responses. Highly purified CD4 + T cells from healthy donors were stimulated with immobilized anti-CD3 with or without IFN-a and IL-12 in the complete absence of accessory cells. IFN-a suppressed CD154 protein and mRNA expression in CD4 + T cells at the initial phase of activation with immobilized anti-CD3, but enhanced it in the subsequent maturation phase irrespective of the presence of IL-12. By contrast, IFNa by itself did not enhance IFN-g production or mRNA expression in CD4 + T cells in the absence of IL-12 even in the presence of stimulation with anti-CD28, but enhanced it in the presence of IL-12. Accordingly, IFN-a enhanced IL-12R b 2 mRNA expression in anti-CD3-stimulated CD4 + T cells. Neither IFNa nor IL-12 influenced the stability of CD154 mRNA in anti-CD3-activated CD4 + T cells. These results indicate that IFN-a by itself enhances CD154 expression in CD4 + T cells independently of the induction of IFN-g mRNA expression. The data also suggest that the optimal induction of human Th1 responses by IFN-a might require the presence of IL-12 and that the induction of Th1 responses and CD154 expression in human CD4 + T cells might be regulated through different mechanisms.

Anti-ribosomal P protein antibody induces Th1 responses by enhancing the production of IL-12 in activated monocytes

“…Thus, IL-12 has been shown to increase the IFN-c production of activated CD4? T cells [19]. Of note, in the present study, anti-IL-12 monoclonal antibodies almost completely abrogated the anti-P-mediated upregulation of the IFN-c production of PBMC, indicating that the enhancement of IFN-c production of PBMC by anti-P requires the presence of IL-12 produced by monocytes.…”

“…Autoantibodies to ribosomal P proteins (anti-P) are detected in 12-16% of patients with SLE [1]. Anti-P are directed to 3 phosphoproteins (P0, P1, and P2), which are located on the larger 60S subunit of eukaryotic ribosomes, and have molecular weights of 38,19, and 17 kDa, respectively [1]. Anti-P have been shown to react a common linear determinant that is present in the carboxyl-terminal 22-amino acid sequence [1].…”

Differential effects of IFN-α on the expression of various TH2 cytokines in human CD4+ T cells

“…[15][16][17] We have recently revealed that IFN-a by itself did not enhance IFN-g production or mRNA expression in anti-CD3-stimulated human CD4 1 T cells in the absence of accessory cells or exogenous IL-12. 18 Consistently, IFN-a enhanced IL-12 receptor b2 (IL-12Rb2) mRNA expression in CD4 1 T cells. 18 It is therefore indicated that the induction of human T H 1 responses by IFN-a requires the presence of IL-12.…”

Overexpression of Orphan Receptor Tyrosine Kinase <i>Ror1</i> as a Putative Tumor-Associated Antigen in Iranian Patients with Acute Lymphoblastic Leukemia

“…NM 005012) and ␤ -actin -specific primers as described [28] . PCR products were finally visualized by running agarose gel (1.5%) electrophoresis containing ethidium bromide.…”