Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00017 (IFN-gamma)
 28,919 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nervous tissue expression of immunological signal and recognition molecules, as well as lymphoid tissue immune responses after facial nerve trauma was studied in male rats of the Lewis and Brown Norway (BN) strains. In both rat strains nerve transection caused within four days the appearance of IFN-gamma-like immunoreactivity in the cytoplasm of axotomized motor neurons and an induction of MHC class I and II, and CD4 molecules on surrounding glial cells to a similar extent. T lymphocytes also infiltrated the facial nuclei ipsilateral to the axotomy in all animals. The number of autoreactive T cells in superficial cervical lymph nodes, which in response to whole myelin or peptides of myelin basic protein (MBP) secreted IFN-gamma increased markedly after axotomy. This response was more conspicuous in Lewis rats, which are susceptible to experimental allergic encephalomyelitis (EAE), than in BN rats, which are EAE resistant. A proportion of the axotomized Lewis rats also developed widespread perivascular infiltration of mononuclear cells in the CNS, reminiscent of EAE. Hypothetically, a strong expansion of myelin autoreactive IFN-gamma producing T cells secondary to nerve trauma may have immunopathological consequences in genetically predisposed individuals. It is also possible that myelin reactive T cells, whether recruited to the lesioned nerve, could have impact on macrophage function during Wallerian degeneration in the distal stump.
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PMID:Facial nerve transection causes expansion of myelin autoreactive T cells in regional lymph nodes and T cell homing to the facial nucleus. 128 78

Immune mechanisms of possible importance for the development and maintenance of peripheral nerve myelin breakdown in HMSN I were analysed by measuring B- and T-cell activation in blood, bone marrow and cerebrospinal fluid. Patients with polyneuropathies of other etiologies served as one control group and patients with tension headache as another. Flow cytometry of blood and bone marrow mononuclear cells revealed that an increased number of CD3+, CD4+ and CD4- CD8- T-cells expressed a late stage activation marker (Ta1). Analysis of T-cells primed for myelin antigens, by studies of IFN-gamma secretion in response to antigen in vitro, showed that both HMSN I and other polyneuropathy patients had low (but significant) numbers of T-cells recognizing whole PNS-myelin. Increased numbers of IgG- and IgM-producing cells were found in blood and bone marrow in the HMSN I patients. Patients with both HMSN I and the other polyneuropathies had few cells in peripheral blood and in bone marrow producing antibodies binding to P2, MAG and MBP in a solid phase immunospot assay. Many cells in the cerebrospinal fluid produced antibodies against MAG. Thus, there was a strong general activation of B- and T-cells in HMSN I while the immunity directed toward peripheral nerve was only slightly elevated. It is an open question if this immune activation is related to the primary gene defect or a secondary event to the nerve damage. The pathogenetic importance of the immune response in maintaining the nerve damage in HMSN I is unclear.
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PMID:Increased systemic B- and T-lymphocyte responses in hereditary motor and sensory neuropathy (HMSN I). 128 71

Rheumatoid arthritis (RA) is an immune disease in which the pathological immune reaction is thought to be initiated by the presentation of an (auto) antigen or superantigen by MHC class II positive cells to CD4 T cells. These successive immunological events can be studied by the cytokines produced at the different stages. Cytokine secretion by stimulated cells in autologous diluted whole blood has allowed the study of the immune profile characteristic of rheumatoid arthritis. The pattern of RA patient whole blood cells cultured in autologous blood is characterized by hyperactivity of the mononuclear cells with high secretion of IL-1 beta, TNF-alpha and IL-6 and low production of IFN-gamma, in comparison with the normal (N) and osteoarthrosis (OA) populations. The IL-2 secretion pattern is unique, arising from production followed by consumption. This production-consumption turnover is the most elevated in the RA group. The T cells are indeed activated in rheumatoid arthritis but regulatory events suppress some of their functions. A correlation was found between the inflammatory proteins and mediators of cellular immunity and macrophagic function: IL-1 beta and the sedimentation rate; IL-6 and fibrinogen; TNF-alpha and the number of blood monocytes. The secretion of OA-stimulated whole blood cells was similar to RA for two monokines (overproduction of TNF-alpha and IL-6) and different for IL-1 beta, not different from normal in OA. Stimulated whole blood cell cytokine secretion profile from RA and OA groups, was the same as previously observed in synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood: II. Application to rheumatoid arthritis and osteoarthritis. 129 40

The IgA effector sites such as the salivary glands and the intestinal tract contain several distinct T cell subsets which possess unique biologic characteristics. Freshly isolated CD3+ T cells from the salivary glands, the LP region of the small intestine and IELs all harbor T cells which spontaneously produce Th1 (IFN-gamma)- and Th2 (IL-5 and IL-6)-type cytokines. Interestingly, a high frequency of IL-5-producing Th2-type cells is always associated with the occurrence of increased numbers of IgA plasma cells (e.g., the salivary glands and the LP region of the small intestine). Further, the salivary gland CD3+ T cells can be divided into three distinct subsets including those of CD4+, CD8- (12-23%), CD4-, CD8+ (18-25%) and DN (6-16%) T cells. In terms of TCR expression, CD4+, CD8- and DN T cells exclusively expressed alpha/beta TCR and gamma/delta TCR, respectively. One of the unique features of the salivary gland T cells is that like IELs, relatively high numbers of gamma/delta TCR-bearing cells are seen in the CD4-, CD8+ T cell fraction. Since our study has provided important new evidence that these gamma/delta TCR-bearing T cells from IELs of mice orally immunized with TD antigen possess the capability of abrogating oral tolerance to antigen-specific immune responses including the IgA isotype, one can visualize that gamma/delta TCR+ T cells can be essential regulatory T cells which protect (or enhance) alpha/beta TCR+, CD4+ Th cells for maximum IgA responses at IgA effector tissues including the salivary glands, and the gastrointestinal tract in the presence of an active state of systemic unresponsiveness or oral tolerance.
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PMID:Cytokine production and T cell receptor expression by salivary gland T cells and intraepithelial T lymphocytes for the regulation of the IgA response. 129 32

The effects of an anti-CD3 mAb on induction of non-MHC restricted cytolysis was investigated. Peripheral blood mononuclear cells (PBMC) from normal donors (29) and cancer patients (18) were cultured in 100 U/ml of interleukin-2 (rIL-2) with and without anti-CD3 mAb (OKT3, 10 ng/ml) for the first 48 hours of incubation. Thereafter, both PBMC cultures were maintained on rIL-2 up to 20 days. PBMC proliferation was enhanced 17-fold in number by day 20 when anti-CD3 mAb and rIL-2 was present during the first 48 hours but only 3-fold by day 20 when rIL-2 alone was present. Concomitantly anti-CD3 mAb but not Lym-1, an isotype matched control, inhibited the induction of lytic activity against both NK sensitive (K562) and NK resistant (Raji) target cell lines. Thus the inhibitory effect is dependent on anti-CD3 mAb stimulating the CD3/TCR T-cell receptor complex. While lytic activity was dependent on the concentration of rIL-2, inhibition of the induction phase of non-MHC restricted lytic activity was independent of the concentration of rIL-2. Flow cytometry analysis indicated that treatment with the anti-CD3 mAb increased the percentage of CD3 positive cells, CD4 positive cells and especially CD25 positive cells, but decreased th percentage of CD56 positive cells. Supernatants from anti-CD3 mAb stimulated cultures also inhibited the induction of non-MHC restricted lytic activity. Lymphokine analysis showed that supernatants of anti-CD3 mAb stimulated cultures had higher levels of TNF-alpha and IFN-gamma. However, TNF-alpha and IFN-gamma alone or in combination could not mediate the inhibitory effect. The inhibitory factor(s) was partially purified by sequential chromatography on matrices of controlled pore glass and Sepharose CL-6B. The molecular weight of the inhibitory factor(s) was less than 67K. These studies have identified a novel regulatory pathway controlling non-MHC restricted cytolysis. Perturbation of the T-cell CD3/TCR complex with the anti-CD3 mAb results in the secretion of a soluble mediator that down-regulates the induction of rIL-2 dependent non-MHC restricted cytolysis.
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PMID:The effect of anti-CD3 on the induction of non-MHC restricted cytolytic activity. 129 40

Human monocytes released superoxide anion, prostaglandin E2, leukotriene B4, IL-1, and TNF when exposed to plastic surfaces coated with murine anti-CD3 monoclonal antibody, OKT 3. Stimulation of mediator release by OKT 3 was dependent on the amount of antibody immobilized onto wells of plastic tissue culture plates. Soluble antibody or antibody adsorbed to monocytes and reacted with an aggregating ("cross-linking") second antibody failed to induce mediator release. Monocytes "armed" with OKT 3 formed rosettes with T cells in a fashion indistinguishable from that seen between monocytes and T cells sensitized with OKT 3. Monocytes with adsorbed OKT 3 antibodies released IL-1 beta and TNF-alpha when exposed to unsensitized T cells, although increased superoxide release could not be detected. OKT 4a, a murine IgG2a antibody that reacts with a different T cell epitope (CD4), failed to induce cytokine release from monocytes when cross-linked by T cells or a CD4+ T cell line, even in the presence of IL-2 or IFN-gamma. These data indicate that certain antibodies bound to Fc receptors (FcR) of monocytes may trigger monocyte function when reacting with cells bearing the appropriate target antigens. FcR-mediated signaling resulting in mediator release may be involved in initiating or regulating the immune response. Furthermore, systemically administered monoclonal antibodies may induce inflammatory responses and their attendant symptomatologies via their interaction with FcR-bearing inflammatory cells.
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PMID:Stimulation of human monocytes by anti-CD3 monoclonal antibody: induction of inflammatory mediator release via immobilization of Fc receptor by adsorbed immunoglobulin and T-lymphocytes. 133 47

Panels of nickel-specific T-lymphocyte clones (TLC) were prepared from nickel-allergic and non-allergic donors. TLC from both panels showed similar levels of expression of TCR alpha/beta, CD4, CD2, CD25, and CD29 and recognized nickel in association with class II HLA molecules with restriction determinants in HLA-DR, HLA-DP, and HLA-DQ. The lymphokine secretion was analyzed in TLC from both panels upon antigen-specific or non-specific stimulation and was compared with the secretion profiles of representants of pre-established human atopen-specific Th1 and Th2 cells. Nickel-specific TLC from both panels showed a lymphokine secretion pattern similar to the atopen-specific Th1 cells, although there was some variation from clone to clone. Most TLC secreted substantial amounts of IFN-gamma, IL-2, TNF-alpha, and GM-CSF, but little or no IL-4 and IL-5. The variation observed mainly concerned IL-2 secretion that could be low or absent in some of the TLC. The general secretion pattern did not change upon different modes of stimulation, including activation via CD3, CD2, or CD28. Because nickel-specific TLC from allergic and non-allergic individuals show a similar Th1 secretion pattern, the present results give no evidence that aberrant lymphokine secretion by CD4+T cells determines the contact allergic state, as was found for atopic allergy in a previous study.
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PMID:Th1 lymphokine production profiles of nickel-specific CD4+T-lymphocyte clones from nickel contact allergic and non-allergic individuals. 134 23

Data from recent studies of murine schistosomiasis mansoni have indicated that certain characteristics of this infection, such as eosinophilia and elevated IgE, are due largely to the induction of Th2-like immune responses by parasite ova. The present study was designed to examine more closely the genesis and development of these skewed Th responses to schistosome eggs. Accordingly, eggs isolated from infected mice were injected s.c. into normal mice. After inoculation, draining lymph node (LN) cells were recovered, phenotyped, and tested for their ability to proliferate and secrete IL-2 and IFN-gamma (as markers of Th1 function) and IL-4, IL-5, and IL-10 (Th2 cytokines). The results show a maximal LN enlargement of 40- to 100-fold by day 3 after egg inoculation. The CD4/CD8/B cell ratio at this time is similar to that in LN from normal mice, but increases in numbers of cells expressing very low levels of MEL-14 and high levels of Pgp-1 are evident by days 3 and 10, respectively. Surprisingly, the initial detectable Ag-specific response to schistosome eggs, observed at day 1, is the production of IFN-gamma. By day 3, LN cells are capable of proliferating and making IFN-gamma plus IL-2, IL-4, IL-5, and IL-10 when stimulated with soluble egg Ag and, therefore, appear Th0-like. After 7 to 10 days, IFN-gamma production is severely depressed but the response continues to be characterized by IL-4, IL-5, IL-10, and IL-2. Depletion studies indicate that CD4 cells are the major population responsible for Ag-mediated proliferation and cytokine production. Results show that schistosome eggs are autonomous inducers of vigorous Th2-like effector responses. Further, our data, from a system that utilizes an in vivo priming step, support the contentions that skewed Th responses develop via an intermediate Th0 stage is accompanied by a loss of the MEL-14 surface marker and an increase in Pgp-1 expression.
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PMID:CD4+ Th2 response induced by Schistosoma mansoni eggs develops rapidly, through an early, transient, Th0-like stage. 134 53

Interaction between the cell adhesion molecules lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) augments T cell activation by increasing the avidity of T cell/antigen-presenting cell (APC) binding. To examine whether LFA-1 and ICAM-1 can also contribute to T cell activation in the absence of APCs, single murine CD4+ and CD8+ T cells were cultured with IL-2 and immobilized antibodies to CD3, CD4 or CD8, and LFA-1 or ICAM-1. The combination of anti-CD3, anti-CD4/CD8, and IL-2 stimulated approximately 20% of CD4+ cells and 30% of CD8+ cells to proliferate. Inclusion of anti-ICAM-1 antibody increased these frequencies to 30 and 40% respectively. Maximum activation frequencies were obtained with the combination of anti-CD3, anti-CD4/CD8, and anti-LFA-1 which stimulated cell division by approximately 40% of single CD4+ cells and at least 60% of single CD8+ cells. Under these conditions, 30-40% of the resultant CD4+ clones and greater than 90% of CD8+ clones secreted IL-3 and IFN-gamma. In addition to responding at higher frequencies that CD4+ cells, CD8+ cells formed larger clones which produced 4-fold higher levels of both cytokines. Although the expression of IL-2, IL-3, IFN-gamma, granulocyte-macrophage colony stimulating factor and tumor necrosis factor alpha could be detected in CD4+ and CD8+ clones at the mRNA level following reverse transcription and polymerase chain reaction amplification, neither the secreted nor mRNA expression of IL-4 or IL-6 was detected in any of the tested clones. It is concluded that co-stimulation of T cells via LFA-1 or ICAM-1 can enhance T cell receptor-dependent activation in the absence of accessory cells and that this mode of stimulation leads to the expression of a restricted range of cytokine genes.
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PMID:Co-engagement of CD3 with LFA-1 or ICAM-1 adhesion molecules enhances the frequency of activation of single murine CD4+ and CD8+ T cells and induces synthesis of IL-3 and IFN-gamma but not IL-4 or IL-6. 135 Apr 61

Activated CD4+ Th2 cells release cytokines (IL-4,-10) that block activation & cytokine (IL-2/IFN-gamma) release by proinflammatory T (CD4+,CD8+) effector cells. To test the hypothesis that peripheral tolerance to alloantigen is linked to differential activation of CD4+ Th2 cells we measured cytokine transcripts in heart grafts (C57BL/10----C3H/HeJ) and spleens of mice rendered "tolerant" by donor-specific blood transfusion, anti-CD4 mAb pretreatment, and cyclosporine administration. The expression of IL-2/IFN-gamma transcripts was reduced greater than 90% in grafts from tolerant recipients. IL-4/IL-10 transcripts were generally enhanced and persisted in graft and recipient spleen. Accordingly adoptive transfer studies were performed to determine whether Th2-like effectors, which express Fc receptors (FcR), mediate suppression in this model. Unfractionated mononuclear cells (MC) (5 x 10(6), isolated from spleens of heart graft recipients made tolerant by DST, prolonged the survival of test grafts greater than 90 days in irradiated (680 rads) recipients reconstituted with a sufficient number of MC from spleens of naive C3H to precipitate rejection of the test graft in 18.2 days (MST, n = 5). Conversely adoptive transfer of inocula depleted of FcR+ cells on immune complex columns or with anti-FcR mAb 24G2 caused test grafts to be rejected in 8-11 days. These results suggest that peripheral tolerance to alloantigen may be linked to differential activation of Th2 cells that induce anergy by suppression. The possibility that Th2-like effectors mediate peripheral tolerance to self is discussed.
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PMID:Heart allografts in murine systems. The differential activation of Th2-like effector cells in peripheral tolerance. 135 22


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