T-CELLS
Contents
Introduction
T celltypes
T-Cell Development
T-Cell Activation
Differentiation and Memory
Introduction
T cell: A type of white blood cell that is of key
importance to the immune system and is at the core of
adaptive immunity.
The T cells are like soldiers who search out and destroy
the targeted invaders.
Immature T cells (termed T-stem cells) migrate to the thymus
gland in the neck, where they mature and differentiate into various
types of mature T cells and become active in the immune system
in response to a hormone called thymosin and other factors.
T-cellsthat are potentially activated against the body's own tissues
are normally killed or changed ("down-regulated") during this
maturational process.
Types of T cell
There are several different types of mature T cells.
Not all of their functions are known.
T cellscan produce substances called cytokines such as the
interleukins which further stimulate the immune response.
T-cellactivation is measured as a way to assess the health of patients
with HIV/AIDS and less frequently in other disorders.
T cellsperform several important functions, which can be divided into two
main categories, namely, regulatory and effector.
The regulatory functions are mediated primarily by helper (CD4-positive) T
cells, which produce interleukins.
The effector functions are carried out primarily by cytotoxic (CD8-positive)
T cells, which kill virus infected cells, tumor cells, and allografts.
T cells are grouped into a series of subsets based on their
function.
CD4 and CD8 T cells are selected in the thymus, but
undergo further differentiation in the periphery to
specialized cells which have different functions.
T cell subsets were initially defined by function, but also
have associated gene or protein expression patterns.
Helper CD4+ T cells
T helper cells (TH cells) assist other lymphocytes, including
maturation of B cells into plasma cells and memory B cells, and
activation of cytotoxic T cells and macrophages.
These cells are also known as CD4+ T cells as they express
the CD4 on their surfaces.
Helper T cellsbecome activated when they are presented
with peptide antigens by MHC class II molecules, which are
expressed on the surface of antigen-presenting cells (APCs).
Once activated, they divide rapidly and
secrete cytokines that regulate or assist the immune
response.
These cells can differentiate into one of several subtypes,
which have different roles.
Cytokines direct T cells into particular subtypes.
Cytotoxic CD8+ T cells
Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-
infected cells and tumor cells, and are also implicated in transplant rejection.
These cells are defined by the expression of CD8 + on the cell surface.
These cells recognize their targets by binding to MHC class I molecules,
present on the surface of all nucleated cells.
CD8+ T cells also produce the key cytokines IL-2 and IFNγ, which influence
the effector functions of other cells, in particular macrophages and NK cells.
Memory T cells
Memory T cells are a subset of infection- and cancer-fighting T
cells (also known as a T lymphocyte) that have previously
encountered and responded to their cognate antigen; thus, the
term antigen-experienced T cell is often applied.
Such T cells can recognize foreign invaders.
Memory T cells may be either CD4+ or CD8+ .
Memory T cells
Memory T cells are long-lived and can expand quickly to
large Regulatory T cells maintain immunological
tolerance by shutting down T cell-mediated immunity
when an immune response is complete and suppressing
autoreactive T cells.
Gamma delta T cells
Gamma delta T cells (γδ T cells) represent a small subset
of T cells which possess a γδ TCR rather than the αβ TCR
on the cell surface.
The majority of T cells express αβ TCR chains.
This group of T cells is much less common in humans
(about 2% of total T cells) and are found mostly in the
gut mucosa.
T cells develop
T cells develop from hematopoietic stem cells (HSC) in the bone
marrow.
Progenitors of those cells migrate to the thymus, here they are known
as thymocytes.
Thymocytes mature in a series of steps based on development of cell
surface markers.
The HSC then differentiate into multipotent progenitors (MPP) which
retain the potential to become both myeloid and lymphoid cells.
The process of differentiation then proceeds to a common lymphoid
progenitor (CLP), which can only differentiate into T, B or NK cells
Myeloid and lymphoid lineages both are involved in dendritic
cell(antigen-presenting cells) formation.
Myeloid cells include monocytes, macrophages, neutrophils,
basophils, eosinophils, erythrocytes, and megakaryocytes to
platelets.
Lymphoid cells include T cells, B cells, and natural killer cells.
Immature T cells do not express either the CD4 or CD8 antigen.
They are known as double-negative (DN) cells (CD4-CD8-).
Through the process of development, they become double-positive
cells (CD4+CD8+), then mature into single-positive (CD4+CD8-
or CD4-CD8+) thymocytes and are released to peripheral tissues.
Most thymocytes die in the process of development.
The remaining 2% become mature T cells.
Double-negative stage
The double-negative stage of T cell development is divided further into
4 stages, DN1-DN4.
based on the presence or absence of other cell surface molecules,
including c-kit (CD117), the receptor for stem cell growth factor;
CD44, an adhesion molecule; and CD25, the chain of the IL-2
receptor
DN1 cells are heterogeneous and may give rise to ɑβ T cells, γδ T
cells, natural killer (NK) cells, dendritic cells, macrophages, or B cells.
Double-positive stage
DP cells that have undergone successful gene rearrangements are subjected
to positive and negative selection in the cortex, and negative selection in
the medulla.
• Positive selection, which selects for those thymocytes bearing receptors
capable of binding self-MHC molecules, resulting in MHC restriction
• Negative selection, which selects against thymocytes bearing high-
affinity receptors for self-MHC/peptide complexes, resulting in self-
tolerance.
Positive selection results in development of CD4+ helper or CD8+
cytotoxic lineages.
Mature CD4+ and CD8+ single-positive cells leave the
thymus and circulate in the blood stream.
γδ T cells do not undergo a positive selection process the
same way that ɑβ T cells do.
The thymic microenvironment
Thymic epithelial cells interact with thymocytes to aid the
development of T cells.
The thymic epithelium produces chemokines, cytokines,
and ligands which promote development of progenitor
cells.
Activation of T cells
T cellsare activated when the T cell receptor is engaged
combined with a costimulatory molecule such as CD28 by the
major histocompatibility complex (MHCII) peptide and
costimulatory molecules of the antigen presenting cells.
Costimulation is necessary for T cell activation.
Once activated, the cell alters expression of its surface proteins.
T cell Activation
Mature T cells are two types:
T cell Activation: CD4+
These cells migrated from the site of
the infection to the lymph nodes.
Activation of these cells requires two signals:
First signal: recognition and binding by TCR and CD4
Second signal (costimutation)
Second signal (costimutation)
These two signals cause activation of T cells.
Activated T cells synthesizes and secretes cytokine IL-2
Summary
