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Exogenous Cytokines (exogenous + cytokine)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2010
William F. Carson
Abstract Immunosuppression following severe sepsis remains a significant human health concern, as long-term morbidity and mortality rates of patients who have recovered from life-threatening septic shock remain poor. Mouse models of severe sepsis indicate this immunosuppression may be partly due to alterations in myeloid cell function; however, the effect of severe sepsis on subsequent CD4+ T-cell responses remains unclear. In the present study, CD4+ T cells from mice subjected to an experimental model of severe sepsis (cecal ligation and puncture (CLP)) were analyzed in vitro. CD4+CD62L+ T cells from CLP mice exhibited reduced proliferative capacity and altered gene expression. Additionally, CD4+CD62L+ T cells from CLP mice exhibit dysregulated cytokine production after in vitro skewing with exogenous cytokines, indicating a decreased capability of these cells to commit to either the TH1 or TH2 lineage. Repressive histone methylation marks were also evident at promoter regions for the TH1 cytokine IFN-, and the TH2 transcription factor GATA-3 in naïve CD4+ T cells from CLP mice. These results provide evidence that CD4+ T-cell subsets from post-septic mice exhibit defects in activation and effector function, possibly due to chromatin remodeling proximal to genes involved in cytokine production or gene transcription. [source]

Everolimus and Basiliximab Permit Suppression by Human CD4+CD25+ Cells in vitro

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2005
David S. Game
Immunosuppressive drugs are essential for the prevention of acute transplant rejection but some may not promote long-term tolerance. Tolerance is dependent on the presence and regulatory function of CD4+CD25+ T cells in a number of animal models. The direct effects of immunosuppressive drugs on CD4+CD25+ cells, particularly those that interfere with IL-2 signaling are uncertain. We studied the effects of the rapamycin derivative everolimus and the anti-CD25 monoclonal antibody basiliximab on the regulatory capacity of human CD4+CD25+ cells in vitro. Both drugs permitted the suppression of proliferation and IFN-, secretion by CD4+CD25, cells responding to allogeneic and other polyclonal stimuli; CTLA-4 expression was abolished on CD4+CD25+ cells without compromising their suppressive ability. Everolimus reduced IFN-, secretion by CD4+CD25, cells before the anti-proliferative effect: this is a novel finding. Exogenous IL-2 and IL-15 could prevent the suppression of proliferation by CD4+CD25+ cells and the drugs could not restore suppression. By contrast, suppression of IFN-, secretion was only slightly impeded with the exogenous cytokines. Finally, CD4+CD25+ cells were more resistant than CD4+CD25, cells to the pro-apoptotic action of the drugs. Together these data suggest that CD4+CD25+ cells may still exert their effects in transplant patients taking immunosuppression that interferes with IL-2 signaling. [source]

Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL and interleukin-15 on the cell surface and promote osteoclastogenesis in autologous monocytes

ARTHRITIS & RHEUMATISM, Issue 4 2006
María-Eugenia Miranda-Carús
Objective To investigate the osteoclastogenic potential of T cells from the peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) on autologous monocytes, and to study the cytokines implicated in this process. Methods T cells and monocytes were isolated from the PB of 20 healthy subjects and 20 patients with early RA, and from the SF of 20 patients with established RA. Autologous T cell/monocyte cocultures were established in the absence of exogenous cytokines or growth factors in order to examine spontaneous ex vivo osteoclast differentiation by tartrate-resistant acid phosphatase staining and calcified matrix resorption activity. Results Surface RANKL was expressed on freshly isolated T cells from the PB of patients with early RA and the SF of patients with established RA. In addition, surface interleukin-15 (IL-15) was detected on freshly isolated T cells and monocytes from the PB of patients with early RA and the SF of patients with established RA. Autologous T cell/monocyte cocultures derived from the SF of patients with established RA and from the PB of patients with early RA, but not from the PB of healthy controls, resulted in osteoclast differentiation that was significantly inhibited by osteoprotegerin (OPG) and by neutralizing monoclonal antibodies to IL-15, IL-17, tumor necrosis factor , (TNF,), and IL-1,. OPG, anti-TNF,, and anti,IL-1, demonstrated a cooperative inhibitory effect. At 1-year followup, surface RANKL and IL-15 and ex vivo osteoclastogenesis were no longer observed on PB T cells or monocytes from patients with early RA in whom clinical remission had been achieved with treatment. Conclusion T cells are important contributors to the pathogenesis of bone erosions in RA through interaction with osteoclast precursors of the monocyte/macrophage lineage. [source]

Thyroid cancer immuno-therapy with retroviral and adenoviral vectors expressing granulocyte macrophage colony stimulating factor and interleukin-12 in a rat model

CLINICAL ENDOCRINOLOGY, Issue 6 2003
Kunihiko Tanaka
Summary background, Introduction of genes encoding immuno-stimulatory cytokine(s) into cancer cells is well known to enhance anti-tumour immunity. aim, The present studies were designed to evaluate the therapeutic efficacy of retroviral- and adenoviral-mediated delivery of IL-12 and/or granulocyte macrophage colony-stimulating factor (GM,CSF) genes for thyroid cancer in an immuno-competent rat model. methods, A rat thyroid cancer cell line FRTL-Tc syngeneic to Fisher rat was used. results, Expression of these exogenous cytokines did not affect in vitro cell growth. Subcutaneous injection of FRTL-Tc cells retrovirally transduced with IL-12 or GM,CSF genes formed significantly smaller tumours than that of the parental cells, but had little effect on growth of distant tumours, suggesting no vaccine effect. Similarly, injection of the cells infected with adenovirus expressing IL-12 or GM,CSF (AdIL-12 or AdGM,CSF) almost completely abolished tumourigenicity and injection of AdGM,CSF into pre-established tumours significantly inhibited growth of the tumours injected; neither, however, showed a systemic vaccine affect. On the other hand, injection of AdIL-12 into the pre-established tumours significantly inhibited growth of not only the tumours injected but also distant tumours, indicating induction of systemic anti-tumour immunity. Serum IL-12 was detectable only in this approach. There was neither a synergistic or additive effect of these two cytokines. conclusions, Our data demonstrate in a rat thyroid cancer model that only injection of AdIL-12 into the pre-established tumours elicited systemic anti-tumour immunity, but injection of AdGM,CSF or injection of the cells expressing IL-12 or GM,CSF elicited only local effect, indicating that in situ delivery of IL-12 gene with adenovirus appears most efficacious but may still require adjuvant modalities to enhance the anti-tumour effect. [source]