Washington, DC: A new control mechanism in our immune system has been
discovered by researchers at Karolinska Institute.
The discovery is of potential significance to the treatment of serious
diseases such as MS (multiple sclerosis), rheumatoid arthritis, and
SLE (Systemic lupus erythematosus).
"Now that we've started to understand the regulatory mechanisms
involved in these autoimmune diseases, we are hopeful that new
treatments can be found," says Mikael Karlsson, associate professor at
the Department of Medicine at Karolinska Institutet in Solna, and one
of the team behind the study now published in the highly reputed
periodical, The Journal of Experimental Medicine.
An important component of our immune defence is a type of cell called
a B cell. Normally, the job of these cells is to produce antibodies,
which in turn bind to and neutralise invasive microorganisms, such as
bacteria and viruses. In people with an autoimmune disease, explains
Dr Karlsson, these B cells actually have an injurious effect and
instead of serving the body, are activated against its own tissues,
which they start to break down.
Patients with SLE and other autoimmune diseases have lower levels of
so-called NKT cells. Previously, it was not known what part these
cells play in the origin and development of the disease; now, however,
the research group at KI has shown that this deficiency is a
contributory pathogenic factor.
"We've demonstrated that NKT cells can regulate how B cells become
activated against healthy tissue, and that a lack of NKT cells results
in greater misguided B cell activation," says Dr Karlsson. "So now we
can mechanically link the NKT cell defect in patients to the disease."
The study also shows that the NKT cells directly impede faulty B cell
activation, and that they do so early in the misdirected process. The
team managed to inhibit the activity of pathogenic B cells by adding
NKT cells - a result that may one day lead to new types of treatment.
http://en.wikipedia.org/wiki/Natural_Killer_T_cell
Natural killer T (NKT) cells are a heterogeneous group of T cells that
share properties of both T cells and natural killer (NK) cells. Many
of these cells recognize the non-polymorphic CD1d molecule, an antigen-
presenting molecule that binds self- and foreign lipids and
glycolipids. They constitute only 0.2% of all peripheral blood T cells.
[1]
Nomenclature
The term “NK T cells” was first used in mice to define a subset of T
cells that expressed the natural killer (NK) cell-associated marker
NK1.1 (CD161). It is now generally accepted that the term “NKT cells”
refers to CD1d-restricted T cells, present in mice and humans,
coexpressing a heavily biased, semi-invariant T cell receptor (TCR)
and NK cell markers.[2] Natural killer T (NKT) cells should not be
confused with natural killer (NK) cells.
Molecular characterization
NKT cells are a subset of T cells that co-express an αβ T cell
receptor (TCR), but also express a variety of molecular markers that
are typically associated with NK cells, such as NK1.1. They differ
from conventional αβ T cells in that their TCRs are far more limited
in diversity and in that they recognize lipids and glycolipids
presented by CD1d molecules, a member of the CD1 family of antigen
presenting molecules, rather than peptide-MHC complexes. NKT cells
include both NK1.1+ and NK1.1-, as well as CD4+, CD4-, CD8+ and CD8-
cells. Natural Killer T cells share other features with NK cells as
well, such as CD16 and CD56 expression and granzyme production.[3][4]
Invariant Natural Killer T (iNKT) cells express high levels of and are
dependent on the transcriptional regulator promyelocytic leukemia zinc
finger (PLZF) for their development.[5][6]
iNKT cells
The best known subset of CD1d-dependent NKT cells expresses an
invariant T cell receptor α (TCR-α) chain. These are referred to as
type I or invariant NKT cells (iNKT) cells. These cells are conserved
between humans and mice and are implicated in many immunological
processes.
Function
Upon activation, NK T cells are able to produce large quantities of
interferon-gamma, IL-4, and granulocyte-macrophage colony-stimulating
factor, as well as multiple other cytokines and chemokines (such as
IL-2 and TNF-alpha).
Significance
NKT cells seem to be essential for several aspects of immunity because
their dysfunction or deficiency has been shown to lead to the
development of autoimmune diseases (such as diabetes or
atherosclerosis) and cancers. NKT cells have recently been implicated
in the disease progression of human asthma.[7]
The clinical potential of NKT cells lies in the rapid release of
cytokines (such as IL-2, IFN-gamma, TNF-alpha, and IL-4) that promote
or suppress different immune responses.
Niciun comentariu:
Trimiteți un comentariu