The effect of surgical immunomodulation on liver inflammation and clearance of DHBV infection

Abstract

The key to developing a therapeutic vaccine for chronic hepadnavirus infection lies in the characteristics of the host-immune response which leads to clearance of acute infection. Groups of 28-day-old ducks which had been surgically bursectomized (n = 10) or thymectomized (n = 13) on the day of hatch or were untreated (n = 21) were inoculated with 10(9) viral genome equivalents (vge) DHBV, then bled twice a week, and euthanased 40 days later. Serum and liver were tested for DHBV DNA and total leukocytes and peripheral blood mononuclear cells (PBMCs) counted. Liver and spleen sections were either stained with hematoxylin and eosin, and graded for inflammation or stained with peroxidase-labeled anti-human CD3 antibody and examined for T lymphocyte distribution. PBMC counts were similar in all groups. DHBV infection combined with bursectomy increased significantly, while thymectomy decreased significantly the total leukocyte count. The spleen and liver bursectomy increased T lymphocyte number while B cells were decreased. Converse changes were observed in thymectomized ducks. Histological evidence of hepatitis was present in infected control and bursectomized ducks but not in the uninfected control or infected thymectomized ducks. In control animals, DHBV challenge caused viremia in 17 and persistent infection in 11 (56%). Fewer thymectomized ducks (3/13, 23%) and significantly more (100%) bursectomized ducks remained persistently infected (P < 0.001). Unexpectedly, bursectomy led to persistence of infection while clearance of infection occurred normally in thymectomized ducks despite decreased T lymphocyte numbers. This suggests that clearance requires T and B lymphocyte collaboration.

Early Nutrition with Different Diets Composition versus Fasting on Immunity-Related Gene Expression and Histomorphology of Digestive and Lymphoid Organs of Layer-Type Chicks

“…At day 14 and 28 PH, the histological examination of the liver revealed the presence of lymphatic cell aggregations that are variable in number and size, and with an uneven scattering in the parenchyma. It has been reported that the hepatic lymphatic aggregations in birds are considered as a part of the peripheral lymphoid tissue that is a key constituent of the lymphatic system due to birds do not have distinctive lymph nodes [44,45]. Lymphoid tissue was recognized in non-immune organs in birds, including liver, pancreas, kidney, endocrine glands, gonads, and the central nervous tissue [43][44][45].…”

“…It has been reported that the hepatic lymphatic aggregations in birds are considered as a part of the peripheral lymphoid tissue that is a key constituent of the lymphatic system due to birds do not have distinctive lymph nodes [44,45]. Lymphoid tissue was recognized in non-immune organs in birds, including liver, pancreas, kidney, endocrine glands, gonads, and the central nervous tissue [43][44][45]. It is still unknown that are these lymphoid tissues a burst of lymphomatosis or a normal reaction of the avian immune system to antigens [46].…”

Clinical Experience with Therapeutic Vaccines Designed for Patients with Hepatitis

“…Depletion studies in chimpanzees, the only other host of HCV besides humans, have shown that both CD4 and CD8 lymphocytes are required for virus elimination [65]. Similar studies conducted in HBV animal models such as ducks also indicate the predominant role of cellular immunity [66]. However, the cellular immune response is also strongly associated with hepatitis, i.e., liver inflammation [67].…”