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 analyse dlymphocytes from DS patients in LFA-1 expression and LFA-1 mediated cell adhesion. DS patients less than 2 years of age expressed a higher level LFA-1 when compared with age-matched controls. The difference in LFA-1 expression was much less significan in older DS patients when compared with age-matched children. Although older children (2-15 year old groups) without DS tend to increase their expression of lymphocyte LFA-1 when compared with younger normal children (0-2 years old), DS patients showed no age-associated increase in lymphocyte LFA-1 expression. Two-color analysis with CD4/CD8 and LFA-1 in patients and controls showed the proportions of CD4+ lymphocytes were comparable in DS patients and controls, while the proportion of CD8+ lymphocytes was higher in older DS patients. Expression levels 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 isofrom were higher in both younge rand older DS patients when compared with age-matched control groups. Noticeably, the LFA-1 expression levels on CD45RO lymphocytes from younger DS patients were higher than the levels of the controls and declined in the older Ds group. We tested lymphocytes (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 β 2 inteegrin expression was comparable with that of normal controls. These results suggest that more generalized pathological processes, such as early senescence of the immune system or ieffective lymphocyte activation, and subsequent integrin dysfunction may underlie the immune defects in DS patients.