Lymphocyte T-Cell Immune Modulator - Discovery and Characterization

Discovery and Characterization

Prior to 1960 the thymus gland, which lies in the cervical thoracic area, was thought to be of little importance. In adult animals the thymus is almost non-existent because it atrophies as animals reach adulthood. It was observed, however, that when pre-adolescent animals are thymectomized they experience a variety of maladies including increased incidence of infection, failure to grow, neuromuscular disorders, cancer, etc., collectively known as “wasting disease”. The greater susceptibility to infection was shown to be directly attributable to a dramatic decrease in peripheral blood lymphocytes in thymectomized animals.

By 1964 it had been demonstrated that regulatory factors extracted from the thymus gland could prevent many of the manifestations of wasting disease. This suggested that the thymus produces substances important in the development of immunity. It was not until 1971 that it was discovered that thymus-derived lymphocytes (T-cells) were important regulators of bone-marrow-derived antibody-producing lymphocytes (B-cells). After the discovery that the thymus was producing profound regulatory factors, several groups of scientists began trying to extract and purify this factor from thymus glands in much the same manner that insulin was prepared from the pancreas for therapeutic use in diabetes. The difficulty was that the thymus is a very small gland and produces very small quantities of the factor. Thus, purification techniques did not allow appropriate pure fractions to be produced in sufficient quantities.

In veterinary medicine, wasting syndrome is also recognized and is thought to be associated with infectious canine hepatitis virus infection, feline infectious peritonitis virus infection, and feline leukemia virus infections. In cases of feline infectious peritonitis, necrotizing lesions in the thymus is often a consequence of early stages of the disease. Additionally, the thymus is a preferred tissue for viral replication of feline immunodeficiency virus, which results in lesions and dysfunction.

In 1983 scientists succeeded in cloning epithelial cell lines from the thymus of various species and began to biochemically and biologically characterize these thymus derived regulatory factors. A protein with a molecular weight of about 50,000 daltons was subsequently described and shown to augment the immune responses of both immature and mature T-cells. This protein came to be known as Lymphocyte T-Cell Immunomodulator (LTCI).