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  • 1
    ISSN: 1432-2277
    Keywords: Key words Cytokine synthesis ; Flow cytometry ; T cells ; Cyclosporine A ; Whole blood
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The availibility of a method to measure the effects of drugs on immune reactivity should be helpful in optimizing treatment after organ transplantation. Since cyclosporine A (CSA) interferes with activation of T cells and cytokine synthesis, production of IL-2 and IFN-γ might constitute a marker of this drug's effects. We measured the capacity for mitogen-stimulated production of these cytokines in whole blood by using immunostaining of intracellular and membrane antigens, followed by flow cytometry. The percentage of CD4+ T cells producing IL-2 or IFN-γ was strongly reduced in 20 transplant patients compared with 24 healthy controls. The capacity for IL-2 production of CD4+ and CD8+ cells correlated inversely with CSA blood levels (P values 0.0087 and 0.0396, respectively). IFN-γ production by CD4+ T cells showed a negative correlation with the prednisolone dose (P = 0.0175) and, for the CD8+ subset, with CSA trough levels (P = 0.0023). These data show that inhibition of T cell cytokine synthesis by CSA and prednisolone can be quantified.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2277
    Keywords: Key words Donor-specific immunological non-responsiveness ; Cytotoxic T cells ; Mixed lymphocyte culture ; Liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since the rate of immunological losses of liver allograft after the immediate posttransplant period is much lower than in other organs, we studied the immune responses against donor HLA antigens in 18 patients with a good long-term outcome to determine whether the development of a state of immunological non-responsiveness to donor antigens might account for this favorable outcome. The reactivity against donor spleen cells was measured before and 2 years after transplantation. The reactivity in mixed lymphocyte culture (MLC) and the frequencies of cytotoxic T cell precursors (CTLp) were determined. Responses against third-party spleen cells were determined concurrently to exclude a generalized reduction of immunocompetence due to chronic immunosuppressive treatment. Before orthotopic liver transplantation, the majority of patients had normal T cell responses against donor antigens that were comparable to those against third-party antigens. Two years after transplantation, donor-specific MLC non-reactivity had developed in 10 of the 18 (56 %) patients. In addition, 15 of 18 (83 %) patients had developed donor-specific cytotoxic T cell (CTL) non-responsiveness; 2 had reduced numbers of CTLp against both donor and third-party cells, while the remaining patient had maintained reactivity against donor antigens. In conclusion, donor-specific non-responsiveness is present in the majority of patients 2 years after successful liver transplantation, but occurs predominantly at the CTL level.
    Type of Medium: Electronic Resource
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