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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

The effect of Cyclosporin A on delayed-type hypersensitivity to a tolerogenic dose of Xenogeneic erythrocytesin the mouse

Webster, L. M. January 1987 (has links)
When administered to mice, by various routes, two days before immunization with a tolerogenic dose (10<sup>9</sup>) of sheep red blood cells, the immunosuppressive drug Cyclosporin A (CsA) prevents the suppression of delayed-type hypersensitivity (DTH) reactions. This was observed over a wide range of CsA doses (5-200 mg/kg), given, in a single dose, from a week before immunization to a day after, and with circulating CsA levels ranging below 45 ng/ml at the time of sensitization or challenge. The augmentation of DTH was characterized by induration, intense mononuclear cell infiltration, increased deposition of <sup>125</sup>I-fibrin within the challenge site and was also reflected in <i>in vitro</i> assays of DTH. Cell transfer experiments showed that the CsA-enhanced DTH could be adoptively transferred to naive recipients, and suggested that CsA may be acting to inhibit a population of Ts cells normally effective during DTH, or to allow T<sub>H</sub>/T<sub>DTH</sub> cell priming. In addition, an increase in L3T4<sup>+</sup> cells (T<sub>H</sub>/T<sub>DTH</sub>) was observed in the CsA-treated mice showing the break in suppression of DTH, suggesting that CsA allowed T<sub>H</sub>/T<sub>DTH</sub> cell priming. The augmented DTH reactions in CsA-treated mice were accompanied by profound inhibition of the production of splenic IgM antibody-producing cells and circulating anti-SRBC antibody levels. CsA was also shown to increase basal and mitogen-induced splenic macrophage procoagulant activity. These observations indicate that this model could prove useful in separation and study of cell-mediated and humoural immunity. In addition, they have important cautionary implications for the continuing investigation of the clinical potential of CsA.

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