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Title: The effect of Cyclosporin A on delayed-type hypersensitivity to a tolerogenic dose of Xenogeneic erythrocytesin the mouse
Author: Webster, L. M.
ISNI:       0000 0001 3565 1477
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1987
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When administered to mice, by various routes, two days before immunization with a tolerogenic dose (109) 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 125I-fibrin within the challenge site and was also reflected in in vitro 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 TH/TDTH cell priming. In addition, an increase in L3T4+ cells (TH/TDTH) was observed in the CsA-treated mice showing the break in suppression of DTH, suggesting that CsA allowed TH/TDTH 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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Immunosuppression with CsA