Interferon

About: Interferon is a research topic. Over the lifetime, 28969 publications have been published within this topic receiving 1219645 citations. The topic is also known as: IFN & interferons.

Interleukin 10 (IL-10) and Viral IL-10 Strongly Reduce Antigen-specific Human T Cell Proliferation by Diminishing the Antigen-presenting Capacity of Monocytes via Dowm'egulation of Class H Major Histocompatibility Complex Expression By Ren6 de Waal Malefyt, John Haanen, Hergen Spits,

Abstract: Summary Interleukin 10 (IL-10) and viral Ibl0 (v-IL-10) strongly reduced antigen-specific proliferation of human T cells and CD4 + T cell clones when monocytes were used as antigen-presenting cells. In contrast, IL-10 and v-Ibl0 did not affect the proliferative responses to antigens presented by autologous Epstein-Barr virus-lymphoblastoid cell line (EBV-LCL). Inhibition of antigen-specific T cell responses was associated with downregulation of constitutive, as well as interferon 3'or Ib4-induced, class II MHC expression on monocytes by IL-10 and v-Ibl0, resulting in the reduction in antigen-presenting of these ceUs. In contrast, IL-10 and v-Ibl0 had no effect on class II major histocompatibility complex (MHC) expression on EBV-LCL. The reduced antigenpresenting capacity of monocytes correlated with a decreased capacity to mobilize intracellular Ca 2 + in the responder T cell clones. The diminished antigen-presenting of monocytes were not due to inhibitory effects of II.-10 and v-Ibl0 on antigen processing, since the proliferative T cell responses to antigenic peptides, which did not require processing, were equaUy well inhibited. Furthermore, the inhibitory effects of Ibl0 and v-IL-10 on antigen-specific proliferative T cell responses could not be neutralized by exogenous Ib2 or Ib4. Although IL-10 and v-IL-10 suppressed IL-lc~, IL-1B, tumor necrosis factor ot (TNF-c~), and IL-6 production by monocytes, it was excluded that these cytokines played a role in antigen-specific T cell proliferation, since normal antigenspecific responses were observed in the presence of neutralizing anti-Ibl, -IL-6, and -TNF-tx mAbs. Furthermore, addition of saturating concentrations of IL-lot, IL-I~, IL-6, and TNF-o~ to the cultures had no effect on the reduced proliferative T cell responses in the presence of Ibl0, or v-Ibl0. Collectively, our data indicate that IL-10 and v-IL-10 can completely prevent antigen-specific T cell proliferation by inhibition of the antigen-presenting capacity of monocytes through downregulation of class II MHC antigens on monocytes.

Virus interference. II. Some properties of interferon.

Abstract: Interferon could be titrated by the amount of interference induced in fragments of chorioallantoic membranes challenged with influenza A virus. Over a ten-fold range, inverse proportion between interferon concentration and haemagglutinin titre reached by the challenge virus was observed. Interferon proved stable at 2 degrees C for 2 weeks. Marked inactivation took place after 1 h at 60 degrees C. Interferon was not measurably sedimented by 100 000 g for $\frac{1}{2}$ $\text{h}$. It was held back by gradocol filters of a.p.d. $0.6\mu $. It was not dialyzable. Interferon was active against influenza A, Sendai, Newcastle disease and vaccinia viruses. It was not neutralized by anti-MEL rabbit serum and only slightly inhibited by pooled human serum rich in complement-fixing antibody to influenza A soluble antigen.

Protection from cytomegalovirus after transplantation is correlated with immediate early 1–specific CD8 T cells

Abstract: T cells are crucial for the control of cytomegalovirus (CMV) in infected individuals. Although CMV-specific T cells can be quantified by various methods, clear correlates of protection from CMV disease have not been defined. However, responses to the pp65 protein are believed to play an important role. Here, the proportions of interferon γ–producing T cells following ex vivo activation with pools of overlapping peptides representing the pp65 and immediate early (IE)-1 proteins were determined at multiple time points and related to the development of CMV disease in 27 heart and lung transplant recipients. Frequencies of IE-1–specific CD8 T cells above 0.2 and 0.4% at day 0 and 2 wk, respectively, or 0.4% at any time during the first months discriminated patients who did not develop CMV disease from patients at risk, 50–60% of whom developed CMV disease. No similar distinction between risk groups was possible based on pp65-specific CD8 or CD4 T cell responses. Remarkably, CMV disease developed exclusively in patients with a dominant pp65-specific CD8 T cell response. In conclusion, high frequencies of IE-1 but not pp65-specific CD8 T cells correlate with protection from CMV disease. These results have important implications for monitoring T cell responses, adoptive cell therapy, and vaccine design.

KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway

Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus linked to the development of Kaposi's sarcoma and a rare B cell lymphoma, primary effusion lymphoma. The KSHV gene ORF K9 encodes vIRF which is a protein with low but significant homology to members of the interferon (IFN) regulatory factor (IRF) family responsible for regulating intracellular interferon signal transduction (Moore PS, Boshoff C, Weiss RA and Chang Y. (1996). Science, 274, 1739-1744). vIRF inhibits IFN-beta signal transduction as measured using an IFN-responsive ISG54 reporter construct co-transfected with ORF K9 into HeLa and 293 cells. vIRF also suppresses genes under IFN regulatory control as shown by inhibition of the IFN-beta inducibility of p21WAF1/CIP1, however, no direct DNA-binding or protein-protein interactions characteristic for IRF repressor proteins were identified. Stable transfectant NIH3T3 clones expressing vIRF grew in soft agar and at low serum concentrations, lost contact inhibition and formed tumors after injection into nude mice indicating that vIRF has the properties of a viral oncogene. Since vIRF is primarily expressed in KSHV-infected B cells, not KS spindle cells, this study suggests that vIRF is a transforming oncogene active in B cell neoplasias that may provide a unique immune escape mechanism for infected cells. This data is consistent with tumor suppressor pathways serving a dual function as host cell antiviral pathways.