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

We searched for a functional marker with which T cells mediating acquired cellular resistance (ACR) can be discriminated from those mediating delayed-type hypersensitivity (DTH) in mice immunized with Mycobacterium bovis BCG. Four wk after injection of the mice with 10(5) viable BCG (vBCG) cells emulsified in IFA, a passive transfer experiment revealed that T cells mediating DTH as well as ACR, which we designated TACR, were generated in the spleen. In contrast, T cells mediating only DTH (TDTH) were generated by immunization with 10(7) killed BCG cells along with IFA. The transferring ability of both TACR and TDTH was substantially reduced by treatment with anti-Thy-1.2 or anti-CD4 mAb plus complement, whereas anti-CD8 treatment had no effect. To determine the functional differences between TACR and TDTH, we assessed IL-2 and IFN-gamma production from TACR and TDTH after stimulation with PPD in vitro. Similar levels of enhanced IL-2 activity were detected in the culture supernatants of both groups of T cells. However, augmented production of IFN-gamma was observed only in TACR. This finding was confirmed by Northern blot analysis for detection of IFN-gamma-specific mRNA. In addition, a significant increase in the number of IFN-gamma-producing cells was observed only in T cells from mice immunized with vBCG. The production of IFN-gamma was also totally abolished by treatment with anti-Thy-1.2 and anti-CD4 mAb plus complement in vitro, whereas anti-CD8 mAb treatment had no effect. These results suggest that CD4+ protective T cells generated by immunization with vBCG are characterized by the ability to produce IFN-gamma after stimulation with specific Ag.
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PMID:IFN-gamma-producing ability as a possible marker for the protective T cells against Mycobacterium bovis BCG in mice. 137 3

We have investigated the effect of soluble recombinant CD4 (sCD4) on the antigen specific (BCG, peptides of mycobacterial 65 kDa hsp) responses of T cell lines of T cell clones. The majority of the antigen specific clones could be suppressed in their antigen driven response by the addition of sCD4, while others, including the parental polyclonal T cell line, were not. The suppression of the specific T cell response was reversed by the addition of anti-CD3, did not affect the proliferative response to IL-2, and was independent of the amount of antigen. A decreased capacity to produce IFN-gamma in response to the antigen by the addition of sCD4 was seen only with those clones that were also inhibited in their specific proliferative response. This model may be used to delineate further the interaction between T cells and the antigen presenting cell, and the finding may limit the possible in vivo use of sCD4 in the therapy of human immunodeficiency virus (HIV) infections.
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PMID:Soluble CD4 suppress the antigen driven proliferative response of certain T cell clones specific for mycobacteria and for peptides by mycobacterial heat shock proteins. 156 92

Growing out of the successful transmission of leprosy to armadillos, making available large quantities of M. leprae, there have been remarkable recent advances in the knowledge of the leprosy bacillus. These bacilli and their isolated chemical constituents provide organisms for in vitro testing of new drugs, reagents for the study of the immunologic dysfunction in leprosy patients, development of early diagnostic methods, and the preparation of candidate vaccines. Leprosy is usually transmitted by the nasorespiratory route, but occasionally, there is transplacental infection. There are reports suggesting that patients have acquired leprosy by contact with wild M. leprae-infected armadillos in Louisiana and Texas. Perturbations in lymphocyte-macrophage interaction appear to be most closely related to the defective CMI in leprosy. The helper T/suppressor T cell populations vary markedly in lesions of the various forms of leprosy, with enhanced suppression of T-cell activity in lepromatous disease. Infiltration of IL-2 and gamma-interferon seems to stimulate CMI in situ in lesions of lepromatous leprosy. Vaccination of lepromatous patients with a killed M. leprae-plus-BCG preparation stimulates CMI and clears tissues of leprosy bacilli, providing an immunotherapeutic approach to the management of leprosy. Immunoprophylactic vaccine trials are in progress, and initial results should be available in 1991. Because of drug resistance, dapsone monotherapy of leprosy is no longer recommended. Multidrug regimens, composed of dapsone, rifampin, and clofazimine or a thioamide, are now required and appear to reduce the incidence of leprosy when applied assiduously. Newer experimental drugs that may eventually be included in these regimens include the fluoroquinolones, minocycline, and clarithromycin. There is no clear evidence that the early serologic diagnosis of leprosy is generally applicable. Favorable response to therapy in multibacillary patients, however, may be assessed by noting drops in levels of M. leprae-specific antigens in blood and urine and, to a lesser extent, levels of specific antibodies in serum. There are conflicting reports on the influence of AIDS on leprosy. There are no convincing data showing that AIDS and leprosy affect each other. Although chemotherapy offers the best current hope for the control of leprosy, effective immunoprophylaxis and improved socioeconomic conditions in endemic areas are thought to be essential in programs for the eradication of leprosy.
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PMID:Leprosy. 173 Jan 74

To search for a potential role of T cell receptor (TcR) gamma/delta T cells in host-defense against mycobacterial infection, we analyzed the kinetics, repertoire, specificity and function of gamma/delta T cells in the peritoneal cavity, lymph node (LN) and spleen during an intraperitoneal infection with a sublethal dose (5 x 10(5)) of viable BCG in mice. The number of bacteria in the organs increased to a maximal level by 28 days after infection, and thereafter decreased gradually. Of the CD3+ cells in PEC on day 7 after infection, approximately 25% were CD4-CD8-, most of which express TcR gamma/delta on their surface. On the other hand, the PEC on day 28 contained an increased number of alpha/beta T cells which were CD4+CD8- or CD4-CD8+ and the proportion of gamma/delta T cells was reciprocally decreased. The kinetics of gamma/delta and alpha/beta T cells in the LN ad spleen during BCG infection are much the same as that seen in the PEC. The early appearing gamma/delta T cells preferentially used V gamma 1/V delta 6 although the repertoire of these T cells are diversified. The gamma/delta T cells in PEC on day 7 remarkably proliferated and produced gamma IFN and IL-2 in response to sonicated BCG or PPD derived from Mycobacterium tuberculosis but not to 65 kd heat shock protein (HSP) derived from M. bovis. These results suggest that gamma/delta T cells precede alpha/beta T cells in appearance during mycobacterial infection and the early appearing gamma/delta T cells may participate in the protection at the early stage against the mycobacterial infection.
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PMID:[Participation of gamma/delta-T cells in the protection against mycobacterial infection]. 183 82

Bovine ocular squamous cell carcinoma (BOSCC) is sensitive to intralesional immunotherapy with BCG or recombinant human IL-2 (rhIL-2). The mechanism of tumor regression is as yet unclear. Alterations in the concentration of IL-2 (and possibly other factors) in the tumor, due to regional injection or induction by BCG, may induce killer cell activity and thus tumor regression. To investigate this, lymphocytes were isolated by mechanical fractionation of biopsies of BOSCC. Growth, phenotypical, and functional characteristics were studied. TIL could be isolated and grown from all biopsies of BOSCC. An estimated increase in cell number of 50-150 fold was observed during 5-7 weeks of culture. FACS analysis of a limited number of the TIL cultures showed a characteristic shift in phenotypes until day 28 of culture. CD2+ cells (50-70%), and as a consequence of this CD2- cells, remained stable in number. The number of CD8+ cells increased. CD4+ cells were detected in low numbers by day 28. Prolonged culture resulted in an increase of CD2- gamma delta + cells, CD2+4-8- cells, and occasionally of both CD8+ and CD2+ cells. In 51Cr release assays TIL showed cytotoxicity for BOSCC-derived tumor cell lines in general, which increased transiently by cocultivation with tumor cells. Killing of YAC-1, and P815 was far less efficient. Preferential killing of autologous cell lines was not seen. In conclusion, TIL from bovine ocular squamous cell carcinomas can be cultured in the presence of rhIL-2, which induces cytotoxic activity for BOSCC-derived tumor cells. Cells responsible for killing in vitro and potentially for regression of the tumor after immunotherapy with BCG or rhIL2 cannot yet be identified. Depletion and blocking experiments are being conducted in order to identify the cells (CD2+8+, CD2-gamma delta + or other CD2 +/-) responsible for killing.
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PMID:Immunotherapy of bovine ocular squamous cell carcinoma: isolation, culture and characterization of lymphocytes present in the tumor. 188 57

Systemic Corynebacterium parvum and BCG have limited activity in gynecologic malignancies. Although intraperitoneal C. parvum is active, its toxicity is prohibitive. Intraperitoneal alpha-interferon is an active second line agent for minimal residual disease following combination chemotherapy. Intraperitoneal interferon trials are ongoing. Alpha-interferon is also active against lower genital tract condyloma acuminata. Sufficient numbers of patients have not been evaluated to determine the activity of interleukin-2(IL-2) in gynecologic malignancies. Radioisotope labeled monoclonal antibodies can image gynecologic malignancies and may have a future therapeutic role. The last decade has witnessed a substantial growth in immunotherapy and has demonstrated a role for biologic agents in cancer therapy. Continued improvement in biologic therapies should lead to major advances in gynecologic cancer diagnosis and therapy.
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PMID:Immunotherapy of gynecologic malignancies. 226 13

Many drugs are applied in local treatment for skin malignant tumors. These drugs are living-BCG, OK-432, MY-1, WPG, interferon preparation (alpha, beta and gamma), TNF, IL-2, peplomycin, bleomycin and others. Some of them already have completed clinical trials and others are under clinical observation. In local administration of these drugs, skin lesions (malignant melanoma, CTL-mainly mycosis fungoides, carcinoma in situ and others) show good improvement. The effects were more observed in the tumors with diameters of 1 cm or less and appeared 3 to 10 injections in most cases. As complications, there are fever, general fatigue, vomiting, anorexia, leucopenia and others. Among them, the fever was most observed immediately after injections without any more severe complications. It may be concluded that treatment by intratumoral administration is useful for skin malignant tumors.
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PMID:[Clinical effects induced by intratumoral administration of anti-cancerous drugs in skin malignant tumors]. 246 39

M. tuberculosis purified protein derivative (Mtb-PPD) as tuberculin, other mycobacterial PPD-preparations and subcellular antigenic extracts of BCG showed varying concentration dependent bimodal effects in lymphoproliferative assay (LA) of Mtb-PPD generated human CD4+ T-cell lines (TCLS). Inhibitory effect on LA by high dose of Mtb-PPD is correlated with the inhibition of IL-2 production during the antigen induced stimulation. Consequently, maximal and inhibitory concentrations of different antigens in dose response LA varied for different TCLS. However, inhibitory effect can be overcome by the high concentration of non inhibitory antigen for the particular TCL. These results indicate that i) dose dependent LA is essential for the evaluation of antigen specificity of TCL; ii) some mycobacterial antigen may induce anergy of certain concentration whereas some others exert positive effect to overcome such anergy related to inhibition or production of IL-2.
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PMID:Concentration dependent functional responsiveness to subcellular antigenic extracts of BCG and different mycobacterial PPDs, of tuberculin (Mtb-PPD) reactive human T-cell lines. 250 78

Many authors tried to show that in lepromatous leprosy (LL), suppressor mechanisms are involved in the immune response. We have previously shown that non-specific suppression (Con A induced) was impaired in LL patients and tends to normalize during the erythema nodosum leprosum episode (ENL). In this system we have shown that CD8+ cells (Leu 2a+) can interfere with the generation of Con A-induced suppression. We also observed that a high percentage of LL patients had an increased spontaneous suppression. In these patients, the number of Leu 2a+ cells added in the assay did not correlate with the suppression values. On the other hand, we had demonstrated that the monocyte suppressor system may have an important role, due to the release of soluble factors (PGE2). We evaluated M. leprae-induced suppressor cell function using a two step assay, on T cell proliferation. The results of this study indicate that the ability of M. leprae to induce suppressor activity was lower in LL patients than in tuberculoid (TT), intermediate clinical forms (BB, BL, BT) and BCG-immunized controls. On the other hand, we determined that the proportion of peripheral blood mononuclear cells (PBMC) bearing the Leu 8+ antigen (associated to suppressor inducer cells) was low in LL and tends to normalize during the ENL episode. Suppression of proliferation could not be overcome with exogenous IL-2 and was not related to the induction of Tac antigen. The ability of LL, TT, ENL and normal cells to proliferate upon PHA or Con A stimulus was similar.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunosuppression in leprosy]. 253 42

The possibility of human B lymphocytes to process and present BCG particulate antigen to BCG specific T cell line was studied. It was found that about 6% of B cells after incubated with BCG for 24 h, showed BCG bacilli in their cytoplasm, by acid fast stain, and became obscure 48 h later. These results demonstrated that human B lymphocytes could phagocytose, process, and degrade BCG particulate antigen. The BCG pulsed B cells acted as antigen presenting cells to BCG specific T cell line. The proliferation and IL-2 production of specific T cell line were significantly enhanced by BCG pulsed B cell stimulation. It was evident that BCG antigen was presented to T cell lines by B cell. The activity of BCG pulsed B cell was time depending. By treating B lymphocytes with chloroquine which interferes with normal lysosome functions could completely inhibit the proliferation of BCG specific T cell line when B lymphocytes were pulsed with BCG or express of BCG. The results revealed that B cells must process antigen before presenting antigen to T cells. It is concluded that B lymphocytes can phagocytose, process and present relevant determinants of BCG particulate antigen to BCG specific T cell line, and that human B lymphocytes may play an important role in the anti-tuberculous immunity in vivo, at least as antigen presenting cells. To pursue the study of this problem, it is suggested to use B lymphocytes deficient mice as experimental models for further investigation.
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PMID:[Antigen presentation of human B lymphocytes on BCG particulate antigen]. 263 Apr 15


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