Showing papers by "William Borkowsky published in 1979"

Erythrocyte Adenosine Deaminase Deficiency without Immunodeficiency: EVIDENCE FOR AN UNSTABLE MUTANT ENZYME

Abstract: A B S T R A C T Inherited deficiency of the purine salvage enzyme adenosine deaminase (ADA) gives rise to a syndrome of severe combined immunodeficiency (SCID). We have studied a 2.5-yr-old immunologically normal child who had been found to lack ADA in his erythrocytes during New York State screening of normal newborns. His erythrocytes were not detectably less deficient in ADA than erythrocytes ofADASCID patients. In contrast, his lymphocytes and cultured long-term lymphoid cells contained appreciably greaterADA activity than those from patients with ADA--SCID. This residual ADA activity had a normal molecular weight and Km but was markedly unstable at 56°C. His residual erythrocytes-ADA activity also appeared to have diminished stability in vivo. ADA activity in lymphoid line cells of a previously reported erythrocyte-ADA-deficient !Kung tribesman was found to contain 50% of normal activity and to exhibit diminished stability at 56°C. ATP content of erythrocytes from both partially ADA-deficient individuals was detectably greater than normal (12.3 and 6.1 vs. normal of 2.6 nmol/ml packed erythrocytes). However, the dATP content was insignificant compared to that found in erythrocytes of ADA--SCID patients (4001,000 nmol/ml packed erythrocytes). The New York patient, in contrast to normals, excreted detectable amounts of deoxyadenosine, but this was <2% of

Effects of human leukocyte dialysates containing transfer factor in the direct leukocyte migration inhibition (LMI) assay.

Abstract: We report on an evaluation of the direct leukocyte migration inhibition (LMI) test as a potential in vitro assay of Transfer Factor activity. Crude dialysates of human leukocyte extracts containing Transfer Factor (DLE) were observed to cause both antigen-dependent and antigen-independent effects on the migration of nonimmune leukocyte populations. We find that only those DLE preparations that are obtained from donors with intense cutaneous DTH reactions to antigen have the capacity to cause antigen-specific effects consistently, and DLE obtained from donors with moderate or absent cutaneous reactivity are generally not active in this regard. Additionally, this antigen-specific activity of DLE is dose dependent. These two variables are consonant with similar requirements for successful in vivo transfer of cutaneous DTH. The pulsing of nonimmune migrating cell populations with immune DLE for 30 to 60 min is an additional requirement for maximum effects to be achieved. When these experimental conditions are met, there is a strong suggestion that antigen-specific inhibition of migration can be conferred by DLE on nonimmune cell populations, which is concordant with the pattern of cutaneous DTH reactions expressed by the donor of DLE. The data suggest further that the component(s) of DLE responsible for this activity resides in a >3500 m.w. dialysis fraction and it does not behave like a superantigen or a chemotactant in this assay system. When immune DLE is incubated with immune leukocyte populations, the anticipated inhibition of migration in the presence of antigen is not augmented but is abrogated instead. The antigen specificity of such suppressor-like activity is currently under investigation. We conclude that the LMI test appears to provide a suitable in vitro assay to investigate further the nature and mechanism of action of DLE and its components and provide a means of separating the moiety or moieties responsible for antigen-specific effects before in vivo testing.

The Proliferative Response of Human Lymphocytes to Antigen Is Suppressed Preferentially by Lymphocytes Precultured with the same Antigen

Abstract: Human blood lymphocytes activated in vitro with antigen to which the donor is reactive are capable of suppressing the secondary proliferative response of autochthonous fresh cells to antigen. Both antigen-specific and antigen-nonspecific suppression can be detected in each experiment. These suppressor cells act by decreasing the number of lymphocytes entering the proliferative response rather than by slowing or otherwise inhibiting ongoing proliferation. The suppressor cells must be added soon after fresh cells are stimulated with antigen to be effective, but the suppressor cells themselves need not proliferate to exert their effect. Suppressor cells are optimally effective when added in numbers equal to those of the responding population, but still exert a significant effect at one-eighth that number.

Purine and Phosphoribosylpyrophosphate Metabolism of Lymphocytes and Erythrocytes of an Adenosine Deaminase Deficient Immunocompetent Child

Abstract: Purine and Phosphoribosylpyrophosphate Metabolism of Lymphocytes and Erythrocytes of an Adenosine Deaminase Deficient Immunocompetent Child