Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of cyclosporin A (CsA) on the generation of NK cells were studied using syngeneic bone marrow transplanted mice subsequently treated with CsA (BMT/CsA mice). In contrast to a severe reduction in T cells that was reported previously, these mice exhibited a marked enhancement of splenic NK activity. The enhanced NK activity was mediated by NK1.1+, Thy-1- cells as assessed by antibody plus complement treatment, and was concomitant with an absolute increase in the numbers of NK1.1+ cells as assessed by flow cytometry. Because the depletion of host-derived, mature NK cells by injection of anti-asialo GM1 antibody before bone marrow reconstitution did not affect the enhancement of NK activity, CsA appeared to augment the generation of NK cells from bone marrow precursors. To investigate a possible relationship between the enhancement of NK activity and the maturational arrest of T cells in the thymus induced by CsA, mice were thymectomized, followed by irradiation, bone marrow reconstitution, and CsA treatment. These mice exhibited as strong enhancement of splenic NK activity as BMT/CsA mice, suggesting that the CsA-induced effect on NK cells is distinct from its effect on T cell development in the thymus. Taken together, these results are the first demonstration of the positive effect of CsA on NK cell generation and may be of importance in clinical bone marrow transplantation.
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PMID:Effect of cyclosporin A on lymphopoiesis. III. Augmentation of the generation of natural killer cells in bone marrow transplanted mice treated with cyclosporin A. 199 36

Antibodies against T cells are widely used as immunosuppressive agents in clinical therapy. As effector functions of chimeric or humanized anti-T cell antibodies cannot be predicted in vitro, we compared T cell-depleting effects of human isotypes in vivo with their immunosuppressive consequences in a mouse BMT model. This system is based on chimeric antibodies with a mouse pan T cell specificity and human constant regions. To secure optimal immunosuppression, the specificity for Thy-1.2--one of the best-characterized T cell antigens--was selected, as Thy-1.2-specific antibodies prevent graft-versus-host disease in fully mismatched mice. Chimeric mouse anti-Thy-1.2 antibody with the human IgG1 Fc part was found to be equally effective in preventing graft-versus-host disease mortality as the highly protective anti-Thy-1.2 mouse IgG2a isotype, while human IgG3 was far less effective. This was not predictable by measuring the degree of T cell depletion in peripheral blood. T cell depletion in lymph nodes, however, exactly reflected the results obtained in the BMT system. In addition, this system offers the advantage of assessing the influence of reduced antigen density by using heterozygous Thy-1.2 mice.
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PMID:A mouse model for the preclinical evaluation of immunosuppressive effector functions of human isotypes. The human IgG1 isotype is superior to IgG3. 810 76

Allo-chimerism and clonal elimination of self antigen (Ag) (Ia + Mls-1a) reactive V beta 6+ T cells were analyzed and compared between allogeneic bone marrow (BM) chimeras reconstituted with BM cells which had been treated with anti-Thy-1 monoclonal antibody (mAb) plus complement (C) (T- chimeras) and BM chimeras which had been reconstituted with BM cells pretreated with anti-Thy-1 mAb alone (T+ chimeras). When lethally irradiated AKR (Mls-1a) mice were reconstituted with BM cells from B10 or B10 H-2 congenic mice, both T+ and T- chimeras were entirely free of signs of graft-versus-host reaction (GVHR). However, complete replacement of the AKR lymphoid tissues by donor BM cells was accomplished at an early stage in T+ chimeras but not in T- chimeras. On the other hand, clonal elimination of V beta 6+ T cells reactive to the recipient Ag (Mls-1a) was abolished in T+ chimeras but successfully induced in T- chimeras. The V beta 6+ T cells not eliminated in T+ chimeras showed depressed responses against Mls-1a antigens. The findings herein demonstrate that T cells which contaminate a BM inoculum survive in recipient mice after treatment with anti-Thy-1 mAb without C in vitro followed by BMT. The surviving T cells have been estimated to represent fewer than 0.5% of the BM cells inoculated. These cells appear to accelerate the full replacement of recipient lymphoid tissues by donor cells. Furthermore, the T cells which survive in the marrow inoculum influence eventually the development of a tolerant state in the T cell repertoire of the donor.
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PMID:Influence of a small number of mature T cells in donor bone marrow inocula on reconstitution of lymphoid tissues and negative selection of a T cell repertoire in the recipient. 829 67