Immunomodulation by corynebacterium parvum in two strains of guinea-pigs and the effect of cyclophosphamide.

An early immunosuppressive phase in the overall stimulatory effect of Corynebacterium parvum on the immune response of two strains of guinea-pigs to ovalbumin (Oa) is described. Boosters given soon after treatment with C. parvum elicited lower secondary responses than those given later on, the peak secondary antibody titre increasing with the interval between primary immunization and the booster injection. Transfer of blood leukocytes (lymphocytes) of immunized donors to virgin syngeneic recipients showed the cellular nature of this effect. Cells transferred from donors boosted on day 40 after primary immunization showed a mean adoptive response that was 3.5 times less than that of a similar number of cells from donors boosted on day 90. The increase in the immunocompetence and/or memory of the transferred cells was related to the moment of injection of the booster antigen (Ag) and not to the interval between priming and transfer, since cells transferred during the primary response failed to show a parallel increase. The early, lesser enhancement of the secondary response by C. parvum would thus appear to be due to a limitation of the number and/or immunocompetence of memory cells developing after the injection of Ag. A marked strain difference was observed in the response of strain 2 and Hartley guinea-pigs to immunization with C. parvum and Oa, delayed-type hypersensitivity (DTH) being relatively inhibited, and antibody (Ab) production relatively increased in the latter, the reverse being true of strain 2 guinea-pigs. The existence of a suppressor or regulatory mechanism sensitive to cyclophosphamide (Cy) during the development of DTH after C. parvum treatment was established. Cy pretreatment, 250-300 mg/kg i.p., of both strains led to the development of a larger number of positive skin tests in animals given C. parvum i.v. and Oa i.d. but not when C. parvum was injected i.d. mixed with Oa. The inhibition of the migration, in the presence of Ag, of peritoneal exudate cells of Cy-pretreated guinea-pigs was also accelerated and enhanced during the first week of the primary response after i.v. C. parvum.