The nomenclature for T lymphocytes is based on the role of the thymus in the differentiation and maturation of T lymphocytes. The prototypic T-cell disorder in which the thymus is absent, small, or in an aberrant location is DiGeorge syndrome (DGS). Other well-known partial deficiencies in T-cell function include the chromosomal breakage syndromes (CBSs), B-cell and T-cell combined disorders (eg, ataxia telangiectasia [AT]) and Wiskott-Aldrich Syndrome (WAS), which are discussed in separate articles. Similarly, pityriasis lichenoides et varioliformis acuta<span> [2] </span>and other entities linked with or part of T-cell lymphoma spectrum are covered elsewhere.
Partial T-cell disorders typically have limited T-cell defects that predispose patients to more frequent or extensive infections; these disorders often include immune dysregulation that allows autoimmune phenomena, lymphoproliferation, and malignancies. For example, patients with partial DGS rarely lack T-cell function as measured by in vitro T-cell proliferation to nonspecific mitogens. When T-cell function is absent in T-cell disorders, the disorder can be lethal. Conventional clinical management for absent T-cell function consists of immune reconstitution using stem cell or bone marrow transplantation.
Partial T-cell defects commonly cause abnormalities of immune regulation. Thus, T-cell to B-cell communication is defective, with partial defects in antibody production and increased incidence of atopy and autoimmune disorders. Inadequate antibody responses directed against bacterial polysaccharide antigens cause an increased risk for sinopulmonary infections caused by encapsulated organisms. The increased risk for reactive airway disease and thyroiditis in patients with DGS and the high incidence of autoimmune hemolytic anemia in patients with WAS are examples of defective T-cell/B-cell interactions that result in self-reactivity.
T-cell disorders in which autoimmunity and polyendocrinopathy predominate have recently been elucidated, and more will certainly be discovered as pathways for T-cell signal transduction are better understood. Mutations in the CD3+ T-cell complex are associated with autoimmune cytopenias, autoimmune enteropathy, and recurrent sinopulmonary infections. Defects in CD95/Fas and Fas ligand lead to autoimmune cytopenias, lymphadenopathy, and hepatosplenomegaly. A syndrome of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the AIRE gene coding for autoimmune regulator.
Mutations in the gene coding for Foxp3 at chromosome band Xp11.22 are manifested as immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome (also termed X-linked syndrome with polyendocrinopathy, immune dysfunction, and diarrhea [XPID]). Mutations in the gene coding for interleukin 2a receptor (IL-2Ra) have similarly caused diarrhea, candidiasis, and lymphoproliferation.
Knockout and transgenic mice have been developed for specific T-cell disorders and are recognized to have helped predict human genetic disorders.
Partial T-cell immunodeficiencies constitute a heterogeneous cluster of disorders characterized by an incomplete reduction in T-cell number or activity. The immune deficiency component of these diseases is less severe than that of the severe T-cell immunodeficiencies and therefore some ability to respond to infectious organisms is retained. Unlike severe T-cell immunodeficiencies, however, partial immunodeficiencies are commonly associated with hyper-immune dysregulation, including autoimmunity, inflammatory diseases, and elevated IgE production. This causative association is counter intuitive. Immune deficiencies are caused by loss-of-function changes to the T-cell component, whereas the coincident autoimmune symptoms are the consequence of gain-of-function changes or loss of regulatory functions.