The effects of cyclosporin A on the chicken immune system

Some aspects of the effects of cyclosporin A (CsA) on the chicken immune system are described. High serum levels of CsA could be maintained by i.m. administration of the drug in a neutral oil (Miglyol 812) every three days. After a transient decrease in peripheral blood T lymphocytes, the blood picture remained normal over a dosage period of three weeks. Mitogenic stimulation of the peripheral blood lymphocytes was strongly depressed, however. Whereas there was a trend to decreased primary immune response of T‐dependent (sheep red blood cells, human γ‐globulins) and T‐independent (B. abortus) antigens, high variation in individual response made this trend statistically insignificant, except for the response to B. abortus at a CsA dose of 50 mg/kg. There was also a trend to decreased secondary IgM response to T‐dependent antigens and increased IgM response to the T‐independent antigens. The clearest alteration in secondary humoral response was the block of IgG (+ IgA) response to both categories of antigens. There was only a slight decrease in body weight after 3 weeks of CsA administration, a decrease in the absolute weights of thymus and spleen (but not bursa) at 50 mg/kg and a decrease in relative weight only in the case of the thymus. Despite these changes, the histology of the thymus, particularly the cortex, was normal. The major histological changes were in the spleen where there was a depletion of the periarteriolar lymphytic sheath, a marked increase in granulated cells, a decrease in germinal centers, and the appearance of large numbers of Mott cells. This type of cell was occasionally found in bone marrow and very rarely in liver and the mucosal connective tissue of the bursa, tissues which were otherwise normal. The Mott cell may arise as a result of the changes in T cell subsets leading to an uncontrolled production of nonsecreted immunoglobulins.