Defective Lymphocyte Transformation and Delayed Hypersensitivity in Wiskott-Aldrich Syndrome

Abstract

Patients with the sex-linked recessive Wiskott-Aldrich (W-A) syndrome have impaired antibody responses to carbohydrate and some protein antigens, defective delayed hypersensitivity, and delayed homograft rejection. The in vitro transformation of peripheral lymphocytes of 7 patients and 18 controls was compared using morphologic criteria, radioautography and tritiated thymidine incorporation. Unstimulated W-A lymphocyte cultures showed more “spontaneous” transformation than did cultures of normal lymphocytes (p < 0.025). Their responses to optimal doses of nonspecific stimulants such as phytohemagglutinin (PHA), pokeweed and staphylococcal filtrate were normal. However, suboptimal doses of PHA stimulated W-A lymphocytes significantly less well than normal cells, and the delayed hypersensitivity reactions of the patients to intradermal PHA were also subnormal. Lymphocytes from both immunized normal and W-A subjects failed to respond to purified pneumococcal polysaccharides. Some antigens such as endotoxins, whole heat-killed pneumococci and Brucella abortus stimulated a low but normal proportion of the W-A lymphocytes to transform. In contrast the W-A lymphocyte response to streptolysin-0 was much lower than normal (p < 0.001). Furthermore, despite repeated booster doses, transformation of the patients' lymphocytes with diphtheria and tetanus toxoids remained below normal (p < 0.001). The W-A lymphocyte reactions were also defective both to mitomycin C-treated normal leucocytes, and to homologous W-A leucocytes. These findings indicate that the cellular immune mechanisms of W-A patients are impaired in that they manifest defective lymphocyte transformation, as well as diminished delayed hypersensitivity.