Biomedical Engineering Reference
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T-cell infiltration has been observed in chronically inflamed tissues of SLE patients.
Although the mechanisms underlying the infiltration process from the blood stream to
inflamed sites are not fully characterized, an upregulation of adhesionmolecules, such
as CD44, is associated with T-cell tissue migration [22]. Consequently, it has been
suggested that CD44 may represent a legitimate therapeutic target for SLE [10]. Thus,
CD44 upregulation on T cells and an expansion of peripheral DN T cells may also
represent disease-related biomarkers for SLE [11]. Numerous, other surface markers
and subsets have been reported to correlate with SLE disease activity such as the
involvement of dendritic cell function (DC) and elevated numbers of CXCR3 þ and
CD4 þ T cells in urine [23, 24].
RA is another example of an autoimmune disease well characterized by clinical
research. RA is a chronic inflammatory autoimmune disease occurring in approxi-
mately 1%of adults that begins with swollen joints and ultimately leads to debilitating
joint destruction. Inflammatory cells such as monocytes and neutrophils, together
with T and B cells, infiltrate the synovium in RA patients. Given that lymphocyte
homing and migration are controlled in part by interactions between chemokines and
their receptors, it is not surprising that chemokine receptor imbalances on peripheral
lymphocytes have been reported in RA [25]. The percentage of B cells expressing the
chemokine receptor CXCR5 that is expressed on na ı
ve B cells and plays a role in
homing the secondary lymphoid organs is decreased in RA patients compared to
control groups. In addition, CXCR3, a chemokine receptor for inflammatory che-
mokines that is upregulated during inflammation and plays a role in cellular
recruitment to inflamed tissue, was found to be upregulated on peripheral B cells
from RA patients. Although there was a considerable intersubject variability, this
phenotype (decreased percentage of CXCR5 þ B cells accompanied by an increase in
the expression of CXCR3) is a good candidate for a disease-specific biomarker and
merits more robust evaluation. Correlation between the disease activity and the level
of memory B cells (IgD , CD27 þ ) in the synovium and in the peripheral blood has
also been described for RA patients [26].
Psoriasis is another well-characterized autoimmune disease; it is primarily a
T-cell-mediated inflammatory autoimmune condition. Unlike SLE and RA, psoriasis
research has not found any links to B-cell abnormalities. Psoriasis occurs in
approximately 2-3% of adults and is primarily localized in the skin and less often
in the joints [27, 28]. The pathogenesis includes DC and T-cell activation, differ-
entiation, and expansion. CD2 is a known costimulatory molecule for T-lymphocyte
activation in psoriasis patients that has made anti-CD2 drugs good targeted therapies
for the treatment of psoriasis. There is a correlation between an anti-CD2 drug
treatment and a decrease in T lymphocytes. Specifically, amarked decrease in effector
memory T cells (CCR7 , CD45RA ) in both CD4 þ and CD8 þ T lymphocyte cell
populations is observed. CD4 þ and CD8 þ T-lymphocyte cells are responsible for
IFN- g production, which also decreases alongwith the effector memory T cells. Na ı
ve
T cell (CCR7 þ , CD45RA þ ) and central memory T cell (CCR7 þ , CD45RA )
populations had no sustained decrease in the presence of therapeutics [29]. The latter
makes a strong case for subset-specific targeted therapeutics that do not affect the
overall populations of cells that will reduce the potential for serious adverse events.
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