Modification of delayed-type hypersensitivity reactions to ovalbumin in cyclosporin A-treated guinea-pigs

Abstract

Cyclosporin A (Cs A) administered daily (25 mg/kg per os) to outbred guinea-pigs for 2 weeks following immunization with ovalbumin (OVA; CsA 0-13) caused profound suppression of 14-day delayed-type hypersensitivity (DTH) skin reactions. Very marked impairment of DTH was also found when Cs A was given for the first time 24 hr before skin testing and at 6 and 24 hr thereafter. In contrast, Cs A given on days 0-4 following OVA immunization (Cs A 0-4) caused dose-related potentiation of 14-day skin responses. These changes in the magnitude and character of DTH in vivo were accompanied by striking alterations in lymphocyte transformation responses and in the extent of macrophage migration inhibition and lymphokine production. Whereas Cs A (0-13) caused almost total suppression of the mitogenic responses of lymph node cells to PHA and antigen, OVA-induced migration inhibition and production of the lymphokine inducing macrophage procoagulant activity (MPCA), Cs A (0-4) augmented these responses to OVA, but did not affect lymphocyte transformation or lymphokine production in response to mitogen. Strain 13 guinea-pigs treated with Cs A (0-4) showed depressed Arthus, but augmented DTH responses to OVA. This significant increase in cell-mediated immunity could be passively transferred using spleen and peritoneal exudate cells, suggesting that under these circumstances Cs A (0-4) may interfere with the generation of a population of suppressor cells which regulate DTH reactions in the guinea-pig.