Biology Reference
In-Depth Information
Th2 cells is even less well understood, but it is possible that an elevation in the level
of intracellular cAMP within any CD4 T cell subset is able to affect the cellular
activity of any subset, whereas NE and
2
AR stimulation affects only naïve CD4
T cell and Th1 cell activity, since these subsets express the
2
AR and Th2 cells do
not. In addition, the timing of
2
AR stimulation on a Th1 cell in relation to the time
of cell activation appears to be an important factor affecting cellular activity, with
stimulation prior to activation inhibiting IFN-, but stimulation at the time of, or later
than, activation having no effect or enhancing the level of IFN- secreted.
5.10 CD8
T Cells
CD8
T cells
are adaptive immune cells that mediate specific killing of microbe-
infected cells or tumor cells. Few studies have shown a direct correlation between the
level and timing of NE exposure and/or
2
AR stimulation on CD8 T cell activity,
but a few findings have provided some insight. Exposure of mice to restraint stress
to increase NE levels decreased the generation of a CD8 T cell response to either
herpes simplex virus (HSV) or influenza virus infection, which was partially medi-
ated by a AR-induced mechanism
[116,117]
. In contrast, certain types of physi-
cal and psychological stress in humans elevated NE levels and induced an increase
in CD8 T cell numbers that was blocked by administration of a AR antagonist
[71,118]
. Likewise, acute administration of a
2
AR agonist to healthy subjects for
7 days caused cell numbers to increase; in contrast, chronic administration caused a
decrease
[119]
. However, chronic exposure to a
2
AR agonist in asthmatic individu-
als did not change the number of bronchial CD8 T cells
[120]
, whereas chronic
exposure in HIV-infected individuals increased CD8 T cell numbers
[121]
, sug-
gesting that a disease process may also influence a CD8 T cell response to
2
AR
stimulation when compared to normal cells.
The timing of exposure to NE in relation to the stage of CD8 T cell differen-
tiation may be relevant, just as it seems to be for the CD4 T cell. For example, if
adrenergic ligands were added after the generation of cytolytic T lymphocyte (CTL),
that is, during the effector stage of the response to antigen, a decrease in CTL activity
occurred
[122,123]
that may have been due to a cAMP-induced decrease in the T cell
receptor (TCR)-dependent release of cytotoxic granules
[124]
. In one study, admin-
istration of a monoamine oxidase inhibitor to tumor-bearing rats increased both NE
levels and the percentage of CD8 T cells in the spleen
[125]
. When mice were
depleted of NE before sensitization with trinitrochlorobenzene (TNCB), the genera-
tion of hapten-specific CD8 T cell cytotoxicity decreased upon TNCB challenge
in comparison to controls
[91]
, suggesting that NE is required for the generation of
cytotoxicity after initial antigen exposure. Thus, the role of NE and/or
2
AR stimula-
tion in modulating CD8 T cell activity remains uncertain in both humans and ani-
mals, being both inhibitory and stimulatory, though these changes may be influenced
by the time of
2
AR stimulation in relation to the stage of CD8 T cell differentia-
tion or the time of adrenergic receptor stimulation in relation to T cell activation.
