Lack of age-associated LFA-1 up-regulation and impaired ICAM-1 binding in lymphocytes from patients with Down syndrome

To investigate the role of LFA-1 in the immune defects in DS patients, we a nalysed lymphocytes from DS patients in LFA-1 expression and LFA-1 mediated cell adhesion. DS patients less than 2 years of age expressed a higher lev el of LFA-1 when compared with age-matched controls. The difference in LFA- 1 expression was much less significant in older DS patients when compared w ith age-matched children. Although older children (2-15-year-old groups) wi thout DS tend to increase their expression of lymphocyte LFA-1 when compare d with younger normal children (0-2 years old), DS patients showed no age-a ssociated increase in lymphocyte LFA-1 expression. Two-colour analysis with CD4/CD8 and LFA-1 in patients and controls showed that proportions of CD4 + lymphocytes were comparable in DS patients and controls, while the propor tion of CD8 + lymphocytes was higher in older DS patients. Expression level s of LFA-1 on both CD4 + and CD8 + lymphocytes in younger DS patients were higher when compared with age-matched controls and close to the expression levels in the older DS group. Proportions of memory lymphocytes expressing the CD45RO isoform were higher in both younger and older DS patients when c ompared with age-matched control groups. Noticeably, the LFA-1 expression l evels on CD45RO lymphocytes from younger DS patients were higher than the l evels of the controls and declined in the older DS group. We tested lymphoc ytes (EBV transformed B cells, resting and anti-CD3 stimulated T cells) for cellular adhesion to recombinant ICAM-1 and found that lymphocytes from DS patients were less adhesive, even though their beta2 integrin expression w as comparable with that of normal controls. These results suggest that more generalized pathological processes, such as early senescence of the immune system or ineffective lymphocyte activation, and subsequent integrin dysfu nction may underlie the immune defects in DS patients.