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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant fusion proteins consist of the N-terminal 488 or 513 amino acids of diphtheria toxin joined to human interleukin 2. Initially those fusion proteins were expressed in E. coli under the control of the tox promotor. Western blot analyses showed that E. coli strains bearing the hybrid genes produce 68 kDa or 72 kDa fusion proteins that retain the immunological determinants of both the diphtheria toxin component and the interleukin 2 component. The fusion protein with mol. mass 72 kDa was partially purified by affinity chromatography. The expression of the fusion proteins under the control of the strong promotors was increased (100-fold for tac- promotor) compared to that under the control of the tox promotor. DT-IL2 might be a useful cytotoxic agent in the treatment of diseases involving IL2 receptor-positive cells, such as allograft rejection, graft-versus-host disease, multiple sclerosis et al.
Mol Biol (Mosk)
PMID:[Design and expression of a diphtheria toxin hybrid protein and human interleukin-2 gene in Escherichia coli]. 147 Jan 75

We report a method of sex chromatin analysis of lymphocytes separated from host organs in transfusion-associated graft-versus-host disease (GVHD), which enabled the demonstration of invasion by donor lymphocytes. The lymphocytes examined were separated from deparaffinized tissue blocks of skin, spleen and bone marrow from two female patients with transfusion-associated GVHD by incubation in 0.5% pepsin. The tissues had been removed at autopsy and fixed in formalin. Sex chromatin analysis was performed by fluorescence microscopy on separated lymphocytes stained with 0.005% quinacrine dihydrochloride. By this means Y chromatin-positive (i.e. male) lymphocytes were demonstrated in the skin, spleen and bone marrow of both female patients.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Sex chromatin analysis of lymphocytes invading host organs in transfusion-associated graft-versus-host disease. 290 May 76

A quantitative analysis of the frequencies of autoantibody producing B-cells has been undertaken by producing and analyzing random hybridoma collections generated in fusions with activated B-cells. Activated B-cells were derived from mice injected with LPS and SRBC and normal mice. They were compared to those derived from mice undergoing chronic GVHD. The frequencies of successful fusion events correlate well with the number of activated B-cells used in the fusions, so that it is reasonable to conclude that the hybridoma collections reflect the activated B-cell repertoires in the different animals. The frequencies of hybridomas producing autoantibodies as well as their specificities for self-antigens, were not significantly different between the different collections of hybridomas. Moreover, no difference in VH gene family expression was found in the different collections of autoantibody producing hybridomas. So, the activated autoreactive B-cell repertoires in GVHF1 mice and in normal mice is similar. In contrast to the normal activated autoreactive B-cell repertoires, which make predominantly IgM antibodies, the GVH-activated autoreactive B-cells make predominantly antibodies of the IgG class. Therefore, we conclude that T-cell mediated graft versus host activation does not generally lead to selective expansion of autoreactive B-cells, but appears to play a crucial role in the switch from IgM to IgG production.
Mol Immunol 1988 Nov
PMID:Autoreactive B-cell repertoire in mice with chronic graft versus host disease. 326 80

In this study cell proliferation in Peyer's Patches (PP) and the crypts of Lieberkuhn of the follicle-associated ileal epithelium was analyzed during the development of acute lethal graft-versus-host disease (GVHD) in adult rats. In addition, the effect of thymectomy on GVHD-induced lymphoproliferation was determined by analyzing the 3H-thymidine labeling index in neonatally thymectomized-control and thymectomized-GVHD rats. A significant increase in the 3H-thymidine-labeling index was found in interfollicular (days 2-7), dome (days 5-10), and follicular (days 5-12) regions of PP as well as in associated ileal crypts (days 5-12) of GVHD rats as compared with controls. Thymectomy altered the proliferative response in PP of GVHD rats in that incorporation of 3H-thymidine by follicular and interfollicular cells was significantly lower than in sham-thymectomized GVHD controls during the later stages of the disease. The results suggest a possible role for host thymus-dependent cells in stimulation of or participation in cell proliferation within follicular and interfollicular areas of PP.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:Acute lethal graft-versus-host disease stimulates cellular proliferation in Peyer's Patches and follicle associated ileal epithelium of adult rats. 615 11

We describe a family of six rat monoclonal antibodies which appear to recognize identical or closely related determinants present on virtually all mature human lymphocytes and monocytes, but absent from other blood cells including myeloid and erythroid colony-forming cells. Four IgM antibodies and one IgG2a fix human complement; one IgG2c antibody does so only poorly. All of the antibodies react with lymphocytes from baboons, rhesus and cynomolgus monkeys. However, in all baboons and rhesus monkeys tested, and some cynomolgus monkeys, they also recognize red cells. Nevertheless, in other cynomolgus monkeys reactivity is with lymphocytes only, so these animals will be suitable models for testing the effects of the antibodies in vivo. The antibodies described here could be useful for in vitro removal of lymphocytes from allogeneic marrow grafts (to prevent graft-versus-host disease) or malignant lymphoid cells from autologous grafts (for treatment of leukaemia) and may also find application as general immunosuppressants and for immunotherapy of leukaemia.
Mol Biol Med 1983 Oct
PMID:Removal of T cells from bone marrow for transplantation. Comparison of rat monoclonal anti-lymphocyte antibodies of different isotypes. 639 85

Tumor necrosis factor-alpha (TNF) has been implicated in the pathogenesis of a variety of human diseases including septic shock, cachexia, graft-versus-host disease and several autoimmune diseases. Monoclonal antibodies directed against TNF provide an attractive mode of therapeutic intervention in these diseases. We have generated a murine monoclonal antibody (A2) with high affinity and specificity for recombinant and natural human TNF. To increase its therapeutic usefulness, we used genetic engineering techniques to replace the murine constant regions with human counterparts while retaining the murine antigen binding regions. The resulting mouse-human chimeric antibody should have reduced immunogenicity and improved pharmacokinetics in humans. Molecular analysis of light chain genomic clones derived from the murine hybridoma suggests that two different alleles of the same variable region gene have rearranged independently and coexist in the same hybridoma cell. The chimeric A2 antibody (cA2) exhibits better binding and neutralizing characteristics than the murine A2 which was shown to contain a mixture of two kappa light chains. The properties of cA2 suggest that it will have advantages over existing murine anti-TNF antibodies for clinical use.
Mol Immunol 1993 Nov
PMID:Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. 823 30

Chronic graft-versus-host disease (GVHD) can be induced in B6D2F1 mice by injection of parental DBA/2 lymphoid cells. Stimulation of donor T cells by host MHC antigens leads to the stimulation of host B cells. Little is known of the lymphokines produced during such a reaction. This study was designed to directly measure the levels of mRNA for interferon-gamma (IFN-gamma), interleukin 2 (IL-2), IL-4, IL-5, and IL-10, as well as several other genes, using semiquantitative polymerase chain reaction (PCR). Semiquantitative PCR was reproducible and signals generated were dependent on the amount of specific RNA or cDNA in each reaction. Early during the progression of GVHD (2 days after the first injection of parental cells) there was little increase in IL-10 mRNA, a slight increase in IL-4 mRNA, and a dramatic increase in IL-2 mRNA. In addition, IL-2 bioactivity was demonstrated in supernatants from GVH splenocytes cultured in vitro for 24 h. Later in the response (1 week after the second and final injection of parental cells) IL-4 mRNA levels were elevated as they were earlier while IL-10 mRNA levels were dramatically increased. IL-2 mRNA levels were no different in mice undergoing GVHD than in normal mice at this time. IFN-gamma mRNA was detectable both early and late, although at similar levels in normal mice and mice undergoing GVHD. At both times examined, IL-4 was below the limits of detection by bioassay and IFN-gamma, IL-4, IL-5 and IL-10 were below the limits of detection by ELISA. Further studies showed that a majority of the IL-4 and IL-10 mRNA found elevated in GVH mice were produced by Thy1.2+ T cells, with small amounts from B220+ B cells. In addition, the detectable IFN-gamma mRNA found in GVH mice at this later time also was produced by Thy1.2+ T cells, with small amounts from B220+ B cells.
Mol Immunol 1993 May
PMID:Cytokine gene expression in mice undergoing chronic graft-versus-host disease. 848 82

Graft-versus-host disease (GvHD) is the opposite of graft rejection in that a transplant containing donor lymphocytes attacks the host's skin, liver and gut. This disease can usefully also attack host tumor cells. There is a peculiar distribution of normal tissue targets in epithelial stem cell sites, suggesting that GvHD may be the abnormal counterpart of a physiological growth control system. Efforts to understand how the graft-versus-tumor effect could be therapeutically separated from GvHD require further understanding of the mechanisms involved in GvHD.
Mol Med Today 1996 Mar
PMID:Does graft-versus-host disease attack epithelial stem cells? 879 68

A number of diverse gene therapy strategies are being evaluated in the search for novel therapeutic approaches to leukemia. Antisense oligonucleotides, ribozymes and retroviral vectors are approaches directed at the molecular mechanisms of cancer. Transfer of genes encoding cytokines and human leukocyte antigens (HLAs) could also be used to elicit immunity against tumor cells. Gene marking strategies have been useful in elucidating the biology of disease relapse after autologous bone marrow transplantation. Suicide genes, such as the herpes simplex thymidine kinase gene, have been used to modulate graft-versus-host disease after allogeneic bone marrow transplantation. Although gene delivery remains a major challenge to gene therapy, some modifications have been implemented to overcome this issue. This review will summarize these gene therapy strategies aimed at increasing the survival of patients with leukemia.
Mol Med Today 1997 Jan
PMID:Gene therapy strategies for leukemia. 902 41

The male-specific minor histocompatibility antigen H-Y plays an important role in both graft rejection and graft-versus-host disease following transplantation of male tissue into females that are completely matched at the major histocompatibility loci. The recent identification of two peptides that, in association with the mouse H-2Kk or human HLA B7 major histocompatibility class I molecules, are recognised by H-Y-specific T cells, has provided evidence for the molecular basis for such anti-H-Y responses. These peptides are encoded by the mouse and human homologues of a ubiquitously expressed Y chromosome gene, Smcy, whilst the equivalent peptides encoded by the X chromosome homologues of this gene fail to be recognised. Genetic studies have demonstrated that, as is the case for other minor histocompatibility antigens, peptide epitopes from several closely linked genes may be required to interact in order to elicit a response against H-Y. Definition of the peptides and the genes that encode these epitopes will allow the development of tolerogenic protocols that could specifically down-modulate the response to H-Y and perhaps even other minor histocompatibility antigens.
J Mol Med (Berl) 1997 Feb
PMID:Why do some females reject males? The molecular basis for male-specific graft rejection. 908 28


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