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In-Depth Information
Interleukin-10 (IL-10) :
IL-10 acts inhibiting the activation of macrophages,
being involved in the homeostatic control of innate host immune responses.
It prevents the production of IL-12 and TNF by activated macrophages. Be-
cause IL-12 is a critical stimulus for IFN-
γ
secretion and induces innate and
cell-mediated immune reactions against intracellular pathogens, IL-10 is re-
sponsible for downregulating these reactions. Therefore, it can be thought of
as a regulatory cytokine, decreasing the magnitude of an established immune
response.
3
Regulatory T Cells
The maintenance of immunologic tolerance by natural CD25
+
CD4
+
T
cells was
presented in [9], where autoimmune diseases were induced in normal rodents by
removal of a specific subpopulation of CD4
+
cells. Recently, it was found that
these cells, responsible for the maintenance of self-tolerance, can be identified by
the expression of the
Foxp3
marker [10]. These cells are capable of exerting sup-
pression upon stimulation via the T cell receptor (TCR), and their engagement
in the control of self-reactive cells is related to the recognition of self-antigens in
the normal environment. Besides, once stimulated, the suppression mediated by
CD25
+
CD4
+
regulatory
T
cells mediate is antigen non-specific. Therefore, they
are capable of suppressing the proliferation of T cells specific for the antigen
that lead to their activation, but also other T cells specific for other antigens, a
mechanism known as
bystander suppression
[11].
In this sense, the defining feature of CD25
+
CD4
+
T
reg
cells is the ability to
inhibit the proliferation of other T cell populations
in vitro
. This suppression
requires the activation of the regulatory cell through its TCR, doesn't involve
killing the responder cell and is mediated through a mechanism based on cell
contact or mediated by IL-10 and other cytokines [12] [13].
These cells play a crucial role not only in preventing self-reactive T cells that
have escaped negative deletion from initiating an immune response against self-
antigens. Induced regulatory cells are engaged in the control of a “legitimate”
response in the periphery, preventing local or systemic immunopathology (such
as septic shock), due to the excessive production of pro-inflamatory cytokines by
activated cells [14]. This is an interesting feature, with little exploration available
in the literature. An important work in this line is [15], where the role of Toll-like
receptors (TLRs) in the process of inflamation is discussed. In addition, these
cells are responsible for preventing the complete elimination of the invading
microbe, because its persistency, in low levels, is important for the continuous
stimulation of long-lived functionally quiescent memory cells [5].
The immune system can be studied in a context of infection, characterized
by a response to antigenic pathogens, or in healthy, normal individuals, when
the internal activities of the system are dominant. In both cases, regulatory T
cells play an important role. In the former, these cells are responsible for the
control of both the inflamatory activity and the intensity of the response. In the
latter, they prevent autoimmune diseases, given the existence of self-reactive B
