The thymus gland in secondary immunodeficiency

The microenvironment within the thymus gland and various thymic hormones facilitates the maturation of prothymocytes to functional T lymphocytes. Abnormal thymic morphology is a hallmark feature of several primary and secondary immunodeficiencies. Thymus glands from patients with the acquired immunodeficiency syndrome or graft-vs-host disease and from patients receiving cyclosporine A therapy are depleted of thymocytes, have a striking reduction in thymic epithelial cell mass, and are virtually devoid of Hassall's corpuscles. In malnourished individuals, similar thymic atrophy is present, although the Hassall's corpuscles are present and cystically dilated. Absence of differentiation antigens or anomalous expression of major histocompatibility antigens occurs on thymic epithelial cells in these conditions, and resembles immunologic abnormalities of the thymus in severe combined immunodeficiency. In acquired immunodeficiency syndrome, graft-vs-host disease, and cyclosporine therapy, there is an expression of cytotoxic/suppressor (CD8) lymphocytes. Experimental evidence suggests that in many situations, such cells may cause damage to the thymic epithelium. The damage to the thymic epithelium may alter the thymic microenvironment and contribute to the immune dysfunction observed in these patients. In addition, a damaged microenvironment may hinder therapeutic efforts to reconstitute immunity.