T-cell deficiencies include (a) DiGeorge syndrome, (b) chronic mucocutaneous candidiasis, (c) transient hypogammaglobulinemia of infancy, and (d) common, variable, unclassified immunodeficiency.
Thymic aplasia (DiGeorge syndrome)
The DiGeorge syndrome or thymic aplasia is a classic example of a pure T-cell deficiency. Although the DiGeorge syndrome is a congenital immunodeficiency, it is not hereditarily transmitted. The condition is believed to be caused by an intrauterine infection prior to the eighth week of life, possibly of viral etiology.
It is associated with microdeletions of chromosomal region 22q11. From the immunological point of view, it results due to defective embryogenesis of the third and fourth pharyngeal clefts at 6–8 weeks of fetal life, leading to deficient development of the thymus and parathyroids.
Tetany and hypocalcemia, both characteristics of hypoparathyroidism, are observed in DiGeorge syndrome in addition to the defects in T-cell immunity. Peripheral lymphoid tissues exhibit a deficiency of lymphocytes in thymic-dependent areas.
A defect in delayed-type hypersensitivity is demonstrated by the failure of affected patients to develop positive skin tests to commonly employed antigens, such as candidin or streptokinase and the inability to develop an allograft response. There is also minimal or absent in vitro responsiveness to T-cell antigens or mitogens. Defective cell-mediated immunity may increase susceptibility of the patient to opportunistic infections and render the individual vulnerable to a graft-versus-host reaction in blood transfusion recipients.
However, the B or bursa equivalent-dependent areas, such as lymphoid follicles, show normal numbers of B cells and plasma cells in patients with DiGeorge syndrome. Serum immunoglobulin levels are within normal limits, and there is a normal immune response following immunization with commonly employed immunogens. Considerable success in treatment of DiGeorge syndrome has been achieved with fetal thymic transplants and by the passive administration of thymic humoral factors.
Chronic mucocutaneous candidiasis
Some patients with chronic infection of skin and mucosa with Candida albicans have exhibited a selective deficiency of cell-mediated immunity. Affected individuals develop severe and widespread forms of candidal infections. Skin tests with Candida antigens and in vitro lymphocyte proliferation responses to C. albicans reveal a selective lack of reactivity.
T-lymphocyte functions are normal when tested with other antigens and mitogens. The humoral response to C. albicans is also normal. Symptomatic therapy with antimycotic agents is often unsuccessful.
Transient hypogammaglobulinemia of infancy
This condition is characterized by the hypogammaglobulinemia in infants that occurs due to progressive catabolism of maternal IgG during the second and third months of life. This condition may persist until 2–3 years of age and become progressively more accentuated. In most cases, a deficiency of helper T-cell function appears to be responsible for the delay in immunoglobulin synthesis.
The diagnostic hallmark for this disease is low-for-age circulating immunoglobulin levels. Peripheral blood B lymphocytes are usually normal. Intravenous gamma globulin is indicated until the child’s immunoglobulin levels normalize. With time, most children develop normal immune function.
Common, variable, unclassified immunodeficiency
This condition, also known as late onset hypogammaglobulinemia, includes a large number of cases of primary immunodeficiency with heterogeneous presentations. These conditions show a variable age of onset and patterns of inheritance, whose clinical picture is similar to that of XLA, but with a less severe course of clinical manifestations. T-cell function appears to be deficient in most cases, with abnormally low proliferative responses to T-cell mitogens.
Sinusitis and bacterial pneumonia are the predominant infections in patients with common, variable, unclassified immunodeficiency. Intestinal giardiasis is common. Opportunistic infections caused by Pneumocystis jiroveci, mycobacteria, viruses, and other fungi are also more frequent in these patients. Treatment usually involves administration of intravenous gamma globulin.