Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:BIOD00082 (IL-2)
 29,198 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine helper T cells activated to sheep or horse erythrocyte antigens in vivo have been established as continuous cell lines in culture. T cells require the presence of a T-cell growth factor (TCGF) for continuous proliferation. TCGF purified from murine, rat, or human sources all stimulate murine T-cell growth. The T-cell mitogens concanavalin A and phytohemagglutinin do not stimulate cell proliferation in continuous T-cell lines. All cells that grow in the presence of TCGF express Thy-1 antigens. Helper activity of T-cell lines is both antigen specific and effective for syngeneic or F1 B cells. Supernates from T-cell lines do not contain antigen-specific or nonspecific helper factors. Although several T-cell lines have shown stable helper activity for greater than 50 wk in culture, other cell lines have shown a gradual decline in effector function. The procedure used to establish and maintain proliferation of T cells in culture should be suitable for the selection and growth of antigen-specific effector T cells from each subclass.
 ...
PMID:Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. 9 24

In addition to allowing for the long-term culture of both murine and human cytolytic T lymphocytes, T-cell growth factor (TCGF) functions as the key proliferation-inducing second signal in both T-cell antigen sensitization and mitogenesis. The observation that thymocytes responded normally to T-cell mitogens in the presence of TCGF, prompted the investigation of the effect of TCGF on nude mouse lymphocyte responses in vitro. We found that spleen, lymph node, and bone marrow cells, isolated from nude mice, were incapable of producing TCGF yet responded normally to T-cell mitogen sensitization provided stimulation was conducted in the presence of TCGF. Nude mouse spleen cells were also capable of responding to alloantigen sensitization in mixed lymphocyte cultures (NLMC) conducted in the presence of TCGF. Thy-1 antigen-positive cells harvested from TCGF-supplemented nude mouse MLC effectively mediated the cytolysis of alloantigen-specific target cells as tested in standard 51Cr-release assays. Cytolytic nude mouse effector cells have remained in TCGF-dependent culture for over 3 mo during which they have continued to mediate significant levels of alloantigen-specific cytolytic reactivity. These results suggest that prothymocytes present in nude mice are capable of responding to immunologic stimuli by differentiating, in vitro, into cytolytic T lymphocytes and that furthermore, a major function of the thymus may be to effect the maturation of TCGF-producing cells.
 ...
PMID:The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes. 15 41

Long-term cultures of human cytotoxic T-cell lines (H-CTLL) were established. H-CTLL cells were strictly dependent on growth upon a T-cell growth factor (TCGF) produced by phytohemagglutinin-stimulated normal human peripheral blood lymphocytes. H-CTLL cells were maintained in TCGF-dependent exponential proliferative culture for over 4 mo during which time they continued to mediate stimulator antigen-specific cytotoxicity as measured by a 4-h 51Cr-release assay. H-CTLL cells recovered from cryopreserved stocks and re-established in long-term culture demonstrated similar high levels of antigen-specific cytotoxicity. H-CTLL cells were 95--100% E-rosette positive and expressed normal T and Ia-like cell surface markers. The ability to sustain differentiated antigen-specific T-effector cells in long-term culture may provide a new means for the study of both the mechanism and regulation of T-cell-mediated immunity.
 ...
PMID:Long-term culture of human antigen-specific cytotoxic T-cell lines. 30 89

Monospecific cloned cytolytic T-lymphocyte lines have been created utilizing T-cell growth factor. The clones were found to retain their cytolytic specificity after prolonged culture and monospecific function was demonstrated by subcloning procedures. Thus, detailed studies of the phenotypic and functional characteristics of monospecific, homogeneous, cytolytic T lymphocytes will now be possible.
 ...
PMID:Monoclonal cytolytic T-cell lines. 31 Aug 61

Murine spleen cells activated by concanavalin A (Con A) in culture produce a class of lymphokine molecules which possess biological activity in a number of lymphocyte response assays. Lymphokines with a mol wt of 30,000, as estimated from gel filtration studies, can be resolved into two components which differ by charge, with isoelectric point (pI) values of 4.3 and 4.9, respectively. Both components stimulate (a) the growth of established T-cell lines in culture, (b) the proliferation of thymocytes in the presence of Con A under culture conditions where Con A alone is nonmitogenic, (c) the induction of antibody responses to heterologous erythrocyte antigens in athymic (nude) spleen cultures, (d) the generation of cytotoxic T lymphocytes (CTL) in thymocyte cultures, and (e) the generation of CTL in nude spleen cultures. In each of these culture systems we suggest that the assays are detecting a single class of lymphokine which acts directly on activated T cells. Nonactivated T cells must be stimulated by either antigen or mitogen before becoming responsive to lymphokine, but do not require antigen or mitogen for continued growth with lymphokine. The two molecular species, separable by isoelectric focusing are referred to as the T-cell growth factor (TCGF). A lymphokine, similar in size (30,000 daltons) to TCGF but heterogeneous in charge (pI 3.0--4.0), stimulates immune responses to erythrocyte antigens in T-cell-depleted spleen cultures but has no stimulatory activity in the other lymphocyte assay systems described. The data have been interpreted as showing the two molecular forms of murine TCGF (pI 4.3 and 4.9) are responsible for many of the lymphokine activities described elsewhere as thymocyte mitogenic factor, nonspecific T-cell-replacing factor and killer helper factor or costimulator. The other lymphokine, separable from TCGF by charge, appears to have true T-cell-replacing activity.
 ...
PMID:Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines. 31 87

In an earlier report, it was shown that murine spleen cells cultured with concanavalin A (Con A) released into the culture supernatants helper and suppressor substances for antibody production. The present communication describes the production of rabbit antisera against culture supernates from Con A-activated spleen cells and their use in a plaque assay for mitogen-activated T cells. The plaque assay, utilizing SRBC to which Staphylococcal protein A had been coupled, the developing anti-supernatant antiserum and guinea pig complement, readily detected secreting T cells. The T-cell nature of the plaque-forming cells (PFC) was established principally by the following: (a) the majority of lymphocytes in the centers of plaques were Thy-1-positive by fluroescence; (b) spleen cells depleted of B cells by incubation in plastic dishes coated with rabbit anti-mouse Ig antibody gave greatly enriched PFC responses; (c) anti-Thy-1 and anti-Lyt-2.2 treatment of spleen cells almost completely depleted PFC; (d) T-cell mitogens (Con A and phytohemagglutinin) but not B-cell mitogens (lipopolysaccharides) induced PFC responses; (e) T cells maintained in culture for 10 d with Con A and T-cell growth factor yielded PFC. Kinetic and dose response studies showed that high doses of mitogen induced rapidly appearing T-PFC and the responses peaked at day 1--2 of culture. Lower doses of mitogen-induced PFC required longer periods of incubation for detection, indicating that cell activation and secretion may be different dose-dependent activities of mitogens. Another noteworthy finding was that the antiserum reacted with surface antigens of T-PFC, indicating that secreted products are expressed on the membranes of T cells, offering the possibility of isolating populations of cells with specific secretory potential. Although the precise nature of the T-cell products detected by the antiserum used in this assay are unresolved, 10% of the target-cell-adherent population from spleen cells of BALB/c mice sensitized to L929 cells formed plaques. This suggests that the antiserum has significant activity against the products of cytotoxic T cells, a finding which accords with the activity of anti-Lyt-2.2 serum against mitogen-induced T-PFC. The method clearly offers new possibilities for the analysis of T cells and their products and should provide an important approach to the clonal analysis of lymphokine production.
 ...
PMID:A hemolytic plaque assay for activated murine T cells. 39 85

The cellular immunodeficiency diseases especially those with impaired IL-2 production are successfully treated by every day injection of rhIL-2. IL-2 is also effective on some patients with antibody deficiency probably caused by the lack of T cell help for B cells. Prolonged infection of EB-virus, human immunodeficiency virus, fungi and mycobacteria can be ameliorated by IL-2 treatment. Superoxide production and bacteriocidal activity of the leukocytes from some cases of chronic granulomatous disease are improved by injection of interferon gamma. Succeeding injection of G-CSF is effective to maintain the leukocyte count of congenital neutropenia to the level competent to protect bacterial infections.
 ...
PMID:[Cytokine therapy of immunodeficiency]. 127 43

Protein-tyrosine kinase and protein-tyrosine phosphatase (PTPase) activities are essential for T-cell antigen receptor-mediated signaling. To assess the functional consequences of alteration of the levels of tyrosine phosphorylation in normal human T cells, the effects of vanadate and hydrogen peroxide were studied. In combination, these agents induced tyrosine phosphorylation of cellular substrates, elevated cytosolic free calcium, and induced interleukin 2 receptor (IL-2R) alpha chain expression but not IL-2 secretion. However, anti-CD28 antibody in combination with vanadate and hydrogen peroxide induced IL-2 secretion, consistent with the requirement for a costimulatory signal in the induction of this gene. The effects of vanadate and hydrogen peroxide were enhanced in the absence of the T-cell PTPase, CD45. Thus, acute pharmacologic manipulation of the level of tyrosine phosphorylation in normal T cells correlates with partial, but not full, activation of these cells; in concert with a costimulatory signal provided by perturbation of the CD28 molecule, the complete program of activation is initiated. These agents should prove useful in dissecting signaling pathways involved in the regulation of genes critical to the immune response.
 ...
PMID:Activation of human peripheral blood T lymphocytes by pharmacological induction of protein-tyrosine phosphorylation. 127 75

We have previously reported that the 5-day culture supernatants of peripheral blood mononuclear cells (PBMC) from Dermatophagides farinae (DF) sensitive asthmatics stimulated with 10 ng/ml DF antigen contain eosinophil chemotactic activity (ECA) with an apparent molecular weight greater than 30000 Da. In the present study, we examined the effects of CyA and FK on the ECA. ECA was tested using modified Boyden chamber method. We found that when CyA or FK was added to the culture throughout the experiment, the production of the factors with ECA by PBMC was inhibited in a dose-dependent manner. These inhibitory effects were unchanged by the addition of a sufficient dose of IL-2 to the culture medium. Isoelectrofocusing of the PBMC culture supernatants consistently yielded a major ECF activity at pH 7.0-7.5. The addition of CyA inhibited this major peak. In conclusion, these results suggest that mononuclear cells stimulated with related antigen produce substances which possess ECA and that CyA and FK can block the production of this substance. Therefore, there is a possibility that an immunosuppressive agent may be useful in bronchial asthma therapy by inhibiting the migration of eosinophils.
 ...
PMID:[Inhibitory effects of cyclosporin A and FK-506 on eosinophil chemotactic factor activity in culture supernatants of mononuclear cells from asthmatics]. 128 86

There have been major advances in our understanding of the cellular and humoral immune mechanisms involved in antitumour activities. The characterization of soluble mediators of the immune response and their synthesis as recombinant proteins has led to an explosion of research activity concerning their role as antitumour agents and also as contributors to the pathogenesis of cancer. It is evident that cytokine production is not restricted to cells of the immune system, and that cytokines are involved in a variety of cell regulatory processes ranging from embryonic development to tissue differentiation. Their production by immune cells may enable interactions between the immune system and other homeostatic systems of the body. The therapeutic role of some cytokines such as the interferons and IL-2 in the routine management of gynaecological cancers needs to be investigated further because of their promise as antitumour agents. The study of cytokine production and cytokine receptor expression by cancers is potentially of great therapeutic value. Identification of cytokines that contribute to tumour progression may paradoxically lead to the treatment of cancers by agents that antagonize their biological effects and to rationalization of future trials of cytokine therapy.
 ...
PMID:The immune system and gynaecological cancer. 128 Jan 88


1 2 3 4 5 6 7 8 9 10 Next >>