Effect of T-cell suppression by cyclosporin on primary and persistent infections of infectious bronchitis virus in chickens.

Two-week-old white leghorn (WL) chickens were inoculated intra-nasally with 4.51ogio median ciliostatic doses (CD50) of IBV strain M41. Cyclosporin (CSP) (100 mg/kg body weight) was injected intra-muscularly 3 days before virus infection and every 3 days till day 15 post-infection (p.i.). Significant reduction in proliferation responses of whole blood lymphocytes to a T-cell mitogen, concanavalin A were induced, but not to a B and T-cell mitogen, pokeweed mitogen. Mortality in the IBV + CSP group was 18%, but in the IBV group it was 2%. No significant differences in the total number of virus isolations were seen between the two groups. Virus titres in trachea, lung and kidneys of the T-cell suppressed chickens were slightly higher and histopathological lesions more severe. Thus it appeared that T-cells may play a major role in limiting severity and lethality of IBV infections rather than clearing virus. To confirm this, another experiment was performed in which 2-week-old brown leghorn (BrL) chickens, relatively resistant to IBV were infected with a pool of IBV strains. Mortality was 43% in the IBV + CSP group and zero with IBV alone. Earlier reports using the same pool of IBV strains have shown a mortality of 47% in line 151 chicks, a line sensitive to IBV infection. Thus, a resistant line was induced to behave like a susceptible line by T-cell suppression. Virus titres were always 1 to 3 logs higher in the kidneys of T-cell suppressed BrL chicks. Attempts to induce re-excretion of virus by CSP treatment of WL chickens infected with the IBV strain M41 when 2 weeks old were unsuccessful, but when chicks were infected with the same strain at day-old and given CSP injections from 5 weeks p.i., virus re-excretion was primarily seen from the kidneys and not the caecal tonsil. Thus the kidney appears to be the primary site of IBV persistence. The pathogenesis of the disease in T-cell suppressed chickens is discussed.