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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:382973 |
| Date | January 1987 |
| Creators | Webster, L. M. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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