 T Cell Deficiencies DiGeorge's Syndrome T cell defects can be caused by the failure of development at several places along the pathway. Since T cells mature in the thymus, failure of development or function of this organ will also result in T cell dysfunction. These patients are at great risk when live, attenuated viruses; e.g., attenuated measles virus, are used in vaccinations, since they are not able to prevent the spread of even the attenuated viruses. DiGeorge's syndrome results from partial or complete failure of development of the thymus and parathyroids. In the complete form, there is no para-thormone, calcium regulation is lacking, and the diagnosis may be made within a few hours of birth when the child goes into hypocalcemic tetany. Associated cardiac deformities and abnormal facies may also result in early diagnosis. The patient presents within one or two months with recurrent viral infections and persistent, refractory mucocutaneous candidiasis. Other fungal infections may also be present. The T cell areas in the lymph nodes are depleted and there is usually a mild lymphopenia; the thymic shadow may be absent in a lateral chest x-ray. Blood lymphocytes are not reactive to the T cell mitogens concanavalin A or phytohemagglutinin. Treatment with periodic (about every 3-6 months) injections of thymic hormones has been effective. Transplants of fetal thymic tissue has also been used with some success. Nezelof's Syndrome Nezelof's syndrome (also known as thymic dysplasia) results from defective thymus function; probably some thymic hormone secreting cells are not present or are not functional. The T cells are probably somewhat more mature than those in DiGeorge's syndrome, and treatment with thymic hormones is more successful. However, fetal (prior to the fourteenth week of gestation) thymus transplants are probably the treatment of choice. Nucleoside phosphorylase deficiency is characterized by a severe T cell dysfunction with associated depletion in circulating T cells. The T cells are not responsive in vitro to the normal T cell mitogens. Immunoglobulin levels may be normal, elevated, or decreased. The severity of the disease varies with different patients, but development of recurrent infections may occur as early as 4 months after birth. This rare deficiency results in a severe deficiency including humoral deficiencies since Th cells are also affected. CD3 is the part of the antigen receptor that transduces the signal that antigen has been bound by the antigen receptor. Thus, the T cells are unable to respond to antigen. Ataxia-Telangectasia Ataxia-Telangectasia is an autosomal recessive trait in which there are defects in both the cellular and humoral arms of the immune response. Deficiency or absence of serum and secretory IgA and IgE is common. Other Ig abnormalities, including IgG subclass deficiency, may also be present. Patients usually present in early life to neurologists because of ataxia; recurrent infections and development of telangiectasia occur between the ages of 3 and 8 years. The defect is in a gene involved in repair of DNA breaks. Wiskott-Aldrich Syndrome Wiskott-Aldrich syndrome is an X-linked recessive defect that affects both cellular and humoral immunity. It is characterized by the triad of 1) severe thrombocytopenia often associated with bleeding, 2) recurrent infections with all classes of microorganisms, and 3) eczema. Immunoglobulin levels are variable but most often include a pattern of IgM of about one half of normal, increased IgE and IgA, and normal IgG. Cellular immunity is initially intact but may become profoundly depressed; response to cell mitogens is initially normal. CD43 (sialophorin), a surface glycoprotein, has been reported absent, reduced or abnormal on patient lymphocytes and platelets. It enhances the antigen specific signaling of T cells through its interaction with ICAM-1.
Recent reports of defective CD23 in these patients is also of interest. This protein is a receptor for the Fc piece of IgE (Fc The only really effective treatment has been bone marrow transplant.
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RII). It is found on lymphocytes, monocytes, and platelets, the cells responsible for the triad of symptoms mentioned above. Lack of CD23 may result in early clearance of these cells.