Date of Award:


Document Type:


Degree Name:

Doctor of Philosophy (PhD)



Committee Chair(s)

Reed P. Warren


Reed P. Warren


Frederick J. Post


John R. Simmons


Stanley D. Allen


Mark C. Healey


Individuals with Down syndrome (US) suffer from increased incidence of respiratory infections and lymphoblastic leukemia, and a death rate that is particularly high in the first 5 years of life. Relatively few studies have probed immune parameters in young US children. Primary immune defects in DS may be masked by a degree of immune maturity in adults, and hygienic factors may have an effect on immune capability throughout the years. A study of young children can give clearer evidence of the actual primary immune defects in DS.

Blood samples were drawn from 20 DS children under 6 years old and from age-matched controls. Packed blood cell volume was measured, various blood cell subpopulations were enumerated and differential counts were performed. Several tests of cellular immune function were performed and plasma zinc levels were determined using atomic adsorption spectrophotometry.

Elevated hematocrit levels were observed in the US group. White blood cell counts and proportions of rosette-forming cells were normal in blood from DS children. Altered neutrophil and lymphocyte proportions in DS samples resulted from a depressed number of circulating lymphocytes in the these subjects. This indicated that T cell numbers are low in DS. DS individuals had a low number of circulating OKT4+ T cells which resulted in significantly depressed T4:T8 ratios. Cells from DS subjects exhibited a reduced proliferative response to phytohemagglutinin; a low response to the optimal concentration of concanavalin A was seen with DS samples, but at suboptimal doses the response was normal; suboptimal concentrations of pokeweed mitogen elicited normal responses by cells from DS children. Preliminary results suggest that interleukin-2 (IL-2) production in young children may correlate positively with age and that DS subjects may produce normal or elevated amounts of IL-2. This suggests that IL-2 receptor function may be defective in T cells from DS children. DS children had normal natural killer cell activity and cells from those children were no more sensitive to the augmenting effects of interferon-alpha than cells from control children. Plasma zinc levels in DS appeared to be normal.

These findings not only provide evidence that the primary immune defect in DS involves low levels of T cells, but they show depressed number and function of helper T cells and suggest defective IL-2 receptor expression in DS.