Alemtuzumab (anti-CD52 mAb) provides long-lasting disease activity suppression 
in relapsing-remitting multiple sclerosis (RRMS). The objective of this study 
was to characterize the immunological reconstitution of T cell subsets and its 
contribution to the prolonged RRMS suppression following alemtuzumab-induced 
lymphocyte depletion. The study was performed on blood samples from RRMS 
patients enrolled in the CARE-MS II clinical trial, which was recently completed 
and led to the submission of alemtuzumab for U.S. Food and Drug Administration 
approval as a treatment for RRMS. Alemtuzumab-treated patients exhibited a 
nearly complete depletion of circulating CD4(+) lymphocytes at day 7. During the 
immunological reconstitution, CD4(+)CD25(+)CD127(low) regulatory T cells 
preferentially expanded within the CD4(+) lymphocytes, reaching their peak 
expansion at month 1. The increase in the percentage of TGF-β1-, IL-10-, and 
IL-4-producing CD4(+) cells reached a maximum at month 3, whereas a significant 
decrease in the percentages of Th1 and Th17 cells was detected at months 12 and 
24 in comparison with the baseline. A gradual increase in serum IL-7 and IL-4 
and a decrease in IL-17A, IL-17F, IL-21, IL-22, and IFN-γ levels were detected 
following treatment. In vitro studies have demonstrated that IL-7 induced an 
expansion of CD4(+)CD25(+)CD127(low) regulatory T cells and a decrease in the 
percentages of Th17 and Th1 cells. In conclusion, our results indicate that 
differential reconstitution of T cell subsets and selectively delayed CD4(+) T 
cell repopulation following alemtuzumab-induced lymphopenia may contribute to 
its long-lasting suppression of disease activity.