Biology Reference
In-Depth Information
NE
β
2
AR
β
2
AR
Naive CD4+
T Cell
IFN-
γ
/cell
Th1 Cell
No change in number of
Th1 cells that develop
NE
β
2
AR
β
2
AR
IFN-
γ
, if NE before
activation
IFN-
γ
, if NE after
activation
Naive CD4+
T Cell
Th1 Cell
NC or
Figure 5.4 Effects of NE on naïve and effector CD4
T cell activity and function.
The
naïve CD4 T cell and the Th1 cell both express the
2
AR. Norepinephrine stimulation of the
2
AR on a naïve T cell has no effect on the number of cells that differentiate to Th1 cells, but
increases the amount of IFN- produced per cell. Norepinephrine stimulation of the
2
AR on
a Th1 cell, prior to cell activation, decreases the level of IFN- produced per cell. In contrast,
NE stimulation of the
2
AR on a Th1 cell, after cell activation, either is without effect or
increases the level of IFN- produced per cell.
2
AR specifically to mediate the enhancing effect on the antibody response. With the
development of a model system of purified splenic naïve B cells cultured in the pres-
ence of CD40L and IL-4, the key stimuli required for a B cell to become activated
to make antibody, researchers were able to conduct more mechanistic studies that
bypassed the complicated and uncontrollable model system involving macrophages,
dendritic cells, T cells, and antigen. Data generated using this model system revealed
that
2
AR stimulation activates the classical signaling pathway, which involves an
association of the receptor with stimulatory G-proteins, activation of adenylyl
cyclase, increased intracellular accumulation of adenosine-3-5-cyclic monophos-
phate, and increased PKA activity (reviewed in Refs
[136,137]
). Upon activation,
PKA regulates the activity of multiple targets via phosphorylation, including various
transcription factors, such as CREB
[138]
, which translated into a higher level of
OCA-B binding to the 3immunoglobulin(Ig)H-enhancer region of the IgH locus to
increase the level of IgG
1
produced per B cell, without affecting the number of cells
that switched to produce IgG
1
(see
Figure 5.5
and Refs
[139-141]
).
Via an indirect pathway, NE stimulation of the
2
AR on a B cell up-regulated
expression of the costimulatory molecule CD86 (also known as B7-2), which upon
