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Tumor necrosis factor (TNF) is the primary cytokine which amplifies the expression of type 1 human immunodeficiency virus (HIV-1). The ability of soluble recombinant type I TNF-receptors (TNF-R) of inhibit TNF-alpha-induced HIV-1 expression was investigated. The results showed that a dimer composed of type 1 TNF-R fused to TgG Fc region could restrict the TNF-alpha-induced HIV-1 expression. These results point to the possibility of treating AIDS by limiting the bioactivity of cytokines which enhance the replication and expression of HIV-1.

Objectives: The clinical efficacy of many multiherbal Traditional Chinese Medicines (TCM) is partially attributable to their immunoregulatory properties. In this study we evaluated the effect of eight commonly used, commercially available multiherbal Chinese medicines on T-cell activation. We focused on Yin Zhi Huang (YZH, an injectable herbal medicine commonly used kr the weatment of liver diseases in China), because it was the most potent inhibitor of T-cell activation in our experimental system. The effects of 10 ingredient components of YZH were also evaluated. Methods: [³H] thymidine incorporation assay was used to assess mouse T-cell proliferation after stimulation with latex heads coated with anti-CD3/CD28 antibodies. CD25, CD69, PD-I, and 1-COS expression by purified mouse CD4 T cells treated with plate-hound anti-CD3 antibody and soluble anti-CD28 antihody was analyzed by fluorescent-activated cell sorter (FACS). Cytokine/chemokine production by human peripheral blood mononuclear cells (PBMC) stimulated with staphylococcal enterotoxin B (SEB) was determined by en- zyme-linked immunosorbent assay (ELISA). Results: Among tested herbal medicines, YZH was the most potent inhibitor of T-cell activation. In splenocyte proliferation assays, the inhibitory effect of YZH was dose-dependent, with a 50% inhibition concentration (IC50) of 1:3200-1:1600. Ten (10) purified compounds found in YZH were evaluated kr their activity. Among them, ursolic acid (1-10 p6mol), luteolin (1-10 μmol), baicalein (1-10 μmol), scopran (5-50 μmol), and crocin (5-50 μmol), exhibited dose-dependent inhibition. YZH also inhibited CD25, CD69, PD-I, and ICOS expression by stimulated mouse CD4 T cells. In human PBMCs, YZH inhibited SEB-stimulated cy- tokine (interleukin [IL]-1 IL-2, IL-6, tumor necrosis factor lTNFl-α, interferon IIFNI-γ) and chemokine (IP- 10, MCP-1, MIP-1α and MIP-1β) production in a dose-dependent manner. Conclusion: Our data show for the First time that YZH is a Potent inhibitor of T-cell activation, and this property may he the major mechanism underlying the clinical efficacy of YZH. Our experimental results pave the way for identification of active component(s) and/or analysis of synergistic/additive effect of a YZH ingredient in future studies. [ABSTRACT FROM AUTHOR]

"...It is likely that the leukocyte granulations are in fact secretory products, which the cell dissolves and spreads to the environment as needed", Paul Ehrlich, 1900. Neutrophil granules have long been recognized as mediators of innate host defense. Newly discovered functions for individual granule proteins suggest that granule constituents may also participate in adaptive immune responses. Neutrophil granule-derived cathepsin G, azurocidin/CAP37 and α-defensins have been shown to be chemotactic for mononuclear cells and neutrophils. Analysis of the chemotactic activity of &alpha-defensins shows that they induce CD45RA[sup+] and CD8 T-lymphocyte cell migration at concentrations 10 to 100-fold below that required for direct bactericidal activity. Additionally, α and Β defensins form chemotactic gradients for immature dendritic cells. Recruiting immature dendritic cells to sites of infection is one way for neutrophil granule proteins to initiate adaptive immune responses. Granules found in other leukocytes such as mast cells also contain serine proteases, such as chymase, that are known to chemoattract neutrophils and mononuclear cells. Preliminary evidence suggests that exocytosis of granule-derived products from a variety of leukocytes can mobilize inflammatory cells and immunocytes. Thus, leukocytes granule-derived proteins, more rapidly that chemokines, can mobilize cells that mediate innate host defense and adaptive immunity. [ABSTRACT FROM AUTHOR]

Highlights: [•] Th17 cells express the highest levels of TNF than other Th subsets. [•] Th17 cells most potently stimulate co-transferred Tregs in Rag1 KO mice. [•] This effect of Th17 cells is TNF- and IL-2-dependent. [•] TNF–TNFR2 plays crucial role in reciprocal stimulation of Th17 cells and Tregs. [Copyright &y& Elsevier]

Abstract: Since we have previously shown that dexamethasone (Dex) enhances the proportion of murine Treg cells, we tested the effect of IL-7, a promoter of T cell survival, together with Dex on human CD4+CD25+ Treg cells in an in vitro setting. The results showed that IL-7 in concert with Dex markedly augmented the generation of CD4+CD25+ T cells. To discern the origin of the induced CD4+CD25+ T cells, MACS-purified CD4+CD25−, and CD4+CD25+ cells were cultured in the presence of Dex and/or IL-7 for 4 days. Although two thirds of CD4+CD25− T cells became CD4+CD25+ T cells, they had no suppressive activity. In contrast, the original CD4+CD25+ T cells maintained suppressive activity after Dex/IL-7 treatment, however, there was not a significant expansion in their cell number. Dex and IL-7 did not induce additional Treg cells, but additively induced the expression of the activation marker CD25 by CD4+CD25− T cells. This combination may provide a novel means of priming CD4 T cells to respond to IL-2 and may prove useful in up-regulation of normal immune responses in immune deficient diseases. [Copyright &y& Elsevier]