of the Max - MDC

A
B
C
D
CD39+ Treg cells and multiple sclerosis (MS). The surface marker CD39 is constitutively expressed by Treg cells. Analysis of human
CD4+ T cells by laser scanning confocal microscopy therefore shows a coexpression of CD39 on the cell expressing the Treg-specific
transcription factor Foxp3 (A). Analysis of a larger number of CD4+ cells by flow cytometry revealed, however, that only a subset of
the Foxp3+ Treg cells expresses CD39 (B). The numbers vary between donors but statistical analysis indicated a significantly reduced
frequency of this subset in the blood of MS patients. Compared to healthy controls the number of total Treg cells is only slightly reduced
(C). Utilization of CD39 as additional cell surface marker revealed that MS patients have strikingly lower numbers of CD39+ suppressor
cells in the blood, suggesting a direct involvement of this subset in the control of the disease (D).
(EAE), the animal model of multiple sclerosis (MS), as well
as for human MS the group could establish that the clinical
state of the disease correlates with striking fluctuations in
the number of T REM cells (Figure). In humans these cells are
characterized by the expression of CD39, a nucleotidase on
the cell surface degrading nucleoside di- and triphosphate.
The data suggest that in particular extracellular ATP plays a
crucial role in the immune regulation. As indicator of ‘nonnatural’
(necrotic) cell death it is released through the damaged
cell membrane and triggers various proinflammatory
reactions resulting in the maturation of dendritic cells and
the release of the ‘endogenous pyrogen’ IL-1β. The removal
of extracellular ATP and the subsequent conversion of the
generated AMP into immune-suppressive adenosine by 5’-
exonuclease, another cell surface enzyme expressed by certain
T REM cells, appear to be a major element in orchestrating
anti-inflammatory immune reactions. The inverse correlation
with the manifestation of MS produced the first cellular
marker of the disease and established a novel link between
immune suppression and the evolutionary conserved signalling
pathways based on extracellular ATP. A major part of
the current research is therefore dedicated to the investigation
of the role of this pathway in the control of autoimmune
diseases and its influence on tumour immune surveillance.
Cancer Research 141