Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HLA-D/Dr region in man encodes major determinants which stimulate T lymphocytes to proliferation. The genetic organization of this region is apparently complex and is at present largely unknown. One obstacle is the scarcity and quality of available typing reagents. In an attempt to obtain high quality anti-DR sera, a series of active immunizations was performed between highly selected, healthy unrelated donors and recipients. One recipient (AR8) was immunized using cells incompatible for HLA-A2, B40 (w60), Cw3 and D/DRw6 and readily developed anti-A2 and B40 antibodies but no anti-C, CR, or other antibodies. When tested against his HLA genotypically fully identical brother using te cellular MLC, PLT, or CML techniques before immunization, results were mutually negative as expected. Following immunization, however, AR8 was able to mount MLC, PLT, and possibly CML responses against lymphocytes from the brother while the reverse combinations remained negative. When tested in the family the trait(s) thus identified seems to be maternally inherited. These results suggest the existence of minor histocompatibility determinants encoded from regions not closely linked to HLA. The brother of AR8 and the immunizing donor thus seem to share one or more determinants not possessed by AR8.
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PMID:One-way positive cellular reactions between two HLA-A, B, C, D/DR genotypically identical brothers following active allogeneic immunization. 641 87

Tolerance to major histocompatibility antigens as well as the ability to mount a cytotoxic response to hapten-modified cells of bone marrow donor and host origin was studied in allogeneic radiation chimeras. Lethally irradiated (C57BL/6 X DBA/2)F1 hosts reconstituted with anti-Thy 1.2 + C-treated bone marrow from (C57BL/6 X CBA)F1 mice showed tolerance to the MHC antigens of the three parental strains as measured by MLC and CML assay. The chimeras responded normally to unrelated allogeneic cells. Chimeric animals generated a cytotoxic response to hapten-modified cells of both donor (CBA) and host (DBA/2) haplotypes, as well as to C57BL/6, demonstrating that tolerance to the hapten-presenting host haplotype is sufficient to allow a cytotoxic antihapten response, and that processing through a semiallogeneic host environment does not affect the ability to generate a response to hapten in conjunction with self-determinants. Chimeras failed to mount a cytotoxic response to hapten presented on nontolerated allogeneic spleen cells.
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PMID:Allogeneic radiation chimeras respond to TNP-modified donor and host targets. 644 28

Cell-mediated immune reactions between a patient suffering from acute myelogenous leukaemia (AML) and an HLA-identical sibling were studied in order to characterize the in vitro reactions in MLC and CML prior to bone marrow transplantation. Our results indicated that antigenic differences were detectable between the blasts and the remission lymphocytes. While the normal sibling did not respond in MLC to her HLA-identical sister's remission lymphocytes, there was an anti-blast response. This proliferative response, however, did not lead to the development of detectable cytotoxic cells capable of destroying blast cells. Unrelated individuals, on the other hand, responded strongly both in MLC and CML to the allogeneic tumour blasts and remission lymphocytes of the patient and the lymphocytes of the healthy sibling. The kinetics and magnitude of the MLC response to blast cells was different from that to remission lymphocytes. This response indicated that the blast cells expressed antigenic differences which were recognized in MLC by both the HLA-identical sibling and unrelated individuals. Furthermore, these tumour cells were capable of sensitizing allogeneic, but not syngeneic lymphocytes to become cytotoxic, though they seemed to be more resistant to destruction in CML than normal cells.
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PMID:Cell-mediated immune responses between HLA-identical siblings: recognition of antigenic changes associated with acute myelogenous leukaemia. 644 29

The suppressive effects of four agents on several types of in vitro immune response and on in vitro responses to T and B mitogens were studied comparatively in spleen cells from C57B1/6 mice, previously injected with each of these agents. It was found that the in vitro PFC response to sheep erythrocytes was the most constantly and extensively inhibited: from 56% after treatment with Con A to 85% after treatment with HSA; LPS and C. parvum also provoked a strong inhibition (74-78%). Inhibition of MLC was constant but less effective, ranging from 36% (LPS) to 57% (C. parvum); HSA and Con A depressed it by about 50%. The CML reaction was substantially inhibited by C. parvum (50%), moderately by Con A and LPS (respectively, 23 and 28%) and slightly by HSA (15%). The inhibition of mitogenic response to PHA and LPS varied widely with the agent used: the PHA response was strongly inhibited by Con A (84%) to a lesser extent by C. parvum (54%) and even less by LPS (27%), whereas HSA did not affect it. LPS reactivity was well inhibited by C. parvum (57%), moderately by Con A (25%), slightly by HSA and not at all by LPS. Most of these agents produced a slight but significant prolongation of skin graft survival time. In vitro experiments using mixtures of spleen cells from treated and normal animals showed that these inhibitory effects were mediated by suppressive cells that developed as a result of the treatment used. The degree of inhibition observed in the mixed cultures satisfactorily paralleled the direct inhibition observed in cells from treated animals. The more consistently suppressive agents seemed to be C. parvum and Con A, the effects of the other two (HSA and LPS) on the cellular responses studied were less regular.
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PMID:Non-specific inhibitory processes of immunological and mitogenic cellular responses. 644 6

Lymphocytes from 13 chronic myeloid leukaemia (CML) patients in remission were tested for their ability to differentiate in vitro into a cell population cytotoxic to autochthonous target leukaemic cells. CML remission lymphocytes were cultured in vitro with autochthonous leukaemic cells and allogeneic normal lymphocytes from an unrelated donor, singly or in combination. The cytotoxic lymphocytes obtained after 7 days of culture were tested for their ability to kill autochthonous leukaemic cells in a 3h 51Cr-release assay. It was found that with the allogeneic stimulus alone, cytotoxicity was generated in 5/13 cases, whilst stimulation of lymphocytes with autochthonous leukaemic cells alone induced cytotoxicity in 7/13 cases. In contrast, anti-leukaemic cytotoxicity was shown in 12/13 cases when responder lymphocytes were stimulated with both autochthonous leukaemic and unrelated allogeneic normal lymphocytes. The specificity of cytotoxicity was confirmed using other targets such as autochthonous PHA-transformed lymphoblasts and mouse L1210 cells. In 1/5 cases, CML remission lymphocytes stimulated with autochthonous leukaemic cells showed cytotoxicity to PHA-transformed autochthonous normal lymphoblasts, whilst 1/4 patients showed nonspecific cytotoxicity to L1210 cells when lymphocytes were cultured in MLC or MLTC, as well as in a 3-cell assay.
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PMID:In vitro generation of lymphocytotoxicity to autochthonous leukaemic cells in chronic myeloid leukaemia. 645 Jun 3

T-cells were investigated by the E rosette assay, PHA stimulation, allogeneic MLC and CML responses, in a group of 100 healthy aged people over 70 years old, and compared to young control individuals less than 45 years old. No major difference was found between the two groups, except for PHA stimulation which was significantly reduced in old individuals when low mitogen concentration was used. These observations suggest that only some T cells subsets are affected by ageing, without modification of the total T lymphocyte number. Contrarily, the phagocytic activities of polymorphonuclear cells assessed in a group of 38 aged people were dramatically decreased, using either the NBT test or a direct phagocytosis assay.
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PMID:Immunological studies in human ageing. I. In vitro functions of T cells and polymorphs. 645 27

Radiolabeled preparations of murine surface immunoglobulin have been shown to bind selectively to immunocompetent responder thymus cells. Such bound immunoglobulin (especially IgG) facilitate the mixed lymphocyte culture and cell-mediated lympholysis responses between immunocompetent thymus-cell subsets. Papain digest of IgG also promote alloantigen recognition between immunocompetent thymocytes; most of the activity residues in the Fc piece. The binding of IgG per se does not activate responder thymocytes. Alloantigen-specific MLC and CML responses in vitro appear to require the participation of alloantigen receptors on the responder cell, the expression of alloantigens by the stimulator thymus cells and the binding of B-cell immunoglobulin by the immunocompetent responder thymocytes. When any of these processes are interrupted an alloantigen-specific response is not generated in vitro.
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PMID:Surface IgG-mediated mixed lymphocyte culture and cell-mediated lympholysis responses by immunocompetent thymus cells. 645 34

This report describes the influence of HLA-D/DR antigen disparity upon the level of cytotoxicity in allogeneic in vitro cultures. Allogeneic cultures, between unrelated HLA-D/-DR full house donors, tested in CML gave three different levels of cytotoxicity, termed weak, intermediate and strong cytotoxicity. HLA-D/-DR compatibility predicts weak cytotoxicity and two HLA-B antigen incompatibility predicts strong cytotoxicity. On the contrary, HLA-A antigens have no major influence upon the strength of cytotoxicity. Accepting that the MLC/CML reaction is an in vitro parallel to the in vivo transplantation of allogeneic tissue, the observations are in accordance with the results of HLA-D/-DR matching for graft survival in human renal transplantation.
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PMID:Influence of HLA-D/DR antigen disparity in CTL generation in vitro. 660 61

T-cell suspensions enriched and depleted for the subpopulation with FcR for antigenbound IgG (EA-RFC) have been tested for the responding capacity in MLC/CML. The results reveal that the EA-RFC depleted T cell suspension (enriched for FcR-ve T cells) have a greater proliferative capacity but unchanged cytotoxicity compared to the unfractionated T cell suspensions. On the contrary, the EA-RFC enriched T cell suspensions (enriched for FcR + ve T cells) have only weak proliferative capacity and cytotoxicity. These results indicate that the major part of proliferating T-amplifiers as well as cytotoxic T-precursor cells are FcR-ve. Fractionation of cytotoxic effector cells day six of culture reveal that cytotoxic cells are found among EA-RFC depleted as well as enriched suspensions. The cytotoxic capacity of effector cells was found to be substantially reduced after EA rosette formation due to a blocking and sterical inhibitory influence of the EA complexes on the close effector-target contact necessary for cytotoxicity. These results indicate predominance of FcR + ve cytotoxic T cells. The rosette indicator system used here for identification and definition of FcR cannot separate cytotoxic T-precursor cells and strongly proliferating T-amplifiers found to be FcR-ve. On the contrary, cytotoxic T-effector cells are predominantly FcR + ve.
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PMID:Lymphocyte subpopulations in man: T-cells with FcR for IgG in the allogeneic response in vitro. 697 64

A human T lymphocyte antigen 4A (40,000 daltons) is defined by a monoclonal, complement- (C) fixing, hybridoma-produced antibody (moAb 4A). This antigen, which is identical to the previously reported antigen 3A 1, is expressed at quantitatively different levels on functional subsets of peripheral T lymphocytes as determined by the cell sensitivity to antibody and C. Peripheral T lymphocytes can be divided into two populations: 4A high-density T cells (4A increases), which are killed in vitro by moAb 4A + C, and 4A low-density T cells (4A decreases), which are not affected in vitro by moAb 4A + C treatment. The helper/inducer T cell lineage, defined by moAb Leu 3a, and the cytotoxic/suppressor T cell lineage, defined by moAb Leu 2A, contain both 4A increases and 4A decreases T cell populations. Functional studies by moAb 4A + C treatment show that 1) the 4A increases T cell population contains T helper cells, which are necessary for in vitro antibody production against red cell-bound determinant; 2) the 4A decreases T cell population contains the precursor T cells, which proliferate in vitro in MLC, and the precursor T cells, which are necessary for the in vitro generation of the alloreactive cytotoxic T cells; and 3) the cytotoxic activity of alloreactive T cells generated in CML assay is abrogated by moAb 4A + C treatment; 4) the activation of T cells by PHA and Con A increases the quantitative expression of 4A antigen.
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PMID:Functionally different T lymphocyte subpopulations determined by their sensitivity to complement-dependent cell lysis with the monoclonal antibody 4A. 698 Sep 17


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