peripheral T and B lymphocytes and to a lesser extent by
monocytes, eosinophils, and macrophages [25-27]. CD52 has
minor expression by mature NK cells and hematological stem
cells [28,29]. In addition, the CD52 antigen is generated by
other cells such as the epithelial cells in the epididymis
and duct deferens and is acquired by spermatozoa once
they travel through the genital tract [30]. CD52 antigen
presents as an accessible target for alemtuzumab. In addition,
CD52 is expressed at low concentrations at the surface
of CD34+ hematopoietic cells, parent stem cells for CD52+
lymphocytes [31,32], therefore, use of alemtuzumab is
associated with annihilation of mature lymphocytes without
myeloablation. While the exact biological function of CD52
remains unknown, some evidence suggests that it is involved
in T lymphocyte migration and costimulation [33-36]. The
C-terminal portion of the protein and a part of the GPI are
identified by alemtuzumab, which in turn advances complement
deposition and formation of the membrane attack
complex for induction of cell lysis [complement dependent
cytotoxicity/cytolysis] [37]. Alternatively, alemtuzumab is
believed to promote antibody-mediated cellular cytolysis
because of its IgG Fc region [38]. Another mechanism of
action for lymphocyte depletion by alemtuzumab is lymphocyte
apoptosis in vitro in the absence of complement or other
immune effector cells. Based on this mechanism lymphocyte
apoptosis occurs via a non-classical caspase-independent
pathway (Figure 1) [39]. Lastly, alemtuzumab may activate
caspase-dependent apoptotic mechanisms in order to deplete
lymphocytes [40]. Apart from the remarkable suppressive
effects of alemtuzumab in MS, the fate of B lymphocyte