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Th1
These participate in both cell-mediated immunity and antibody-mediated immunity. They are
essential for controlling such intracellular pathogens as viruses and certain bacteria, e.g.,
Listeria and Mycobacterium tuberculosis (the bacillus that causes TB). They provide cytokine-
mediated "help" to cytotoxic T lymphocytes — perhaps the body's most potent weapon against
intracellular pathogens.
Th2
These provide help for B cells and are essential for the production of IgE antibodies and assist in
the production of some subclasses of IgG as well. Antibodies are needed to control
extracellular pathogens (which — unlike intracellular parasites — are exposed to antibodies in
blood and other body fluids).
Tfh
These also provide help to B cells enabling them to develop into antibody-secreting plasma
cells. This occurs in nests of lymphoid cells — called follicles — in the lymph nodes. The most
abundant helper T cells there are B-cell helpers called follicular helper T (Tfh) cells.
Th17
These protect surfaces (e.g., skin, lining of the intestine) against extracellular bacteria.
In addition, there is another related subset that dampens rather than promotes immune responses. These cells,
designated Treg, are discussed on another page. Link to it.
Th1 Cells
Th1 cells are produced when dendritic cells and pre-Th cells
form an immunological synapse in which the dendritic cell
These
Th2 Cells
Th2 cells are produced when antigen-presenting cells (APCs) present antigen (e.g., on parasitic helminth
worms or certain allergens) to the T cell's receptor for antigen (TCR) along with
The identity of the APCs for Th2 responses is still uncertain. Some research indicates that basophils are the
APCs, but other research questions this role.
Link to graphic showing how Th2 cells stimulate B cells to mature into antibody-secreting plasma cells.
Two transcription factors have been found that play a critical role in the choice between becoming a Th1 or
a Th2 cell.
turning on the genes needed for Th1 function (e.g., for IFN-γ)
blocking the activity of GATA3.
Mice whose genes for T-bet have been "knocked-out" lack Th1 cells and have elevated numbers of Th2
cells (making them susceptible to such Th2-mediated disorders as asthma).
turning on the genes needed for Th2 function (e.g., for IL-5)
blocking the activity of T-bet
IFN-γ (shown above in red) and IL-12 inhibit the formation of Th2 cells;
IFN-γ also inhibits class-switching in B cells.
IL-4 kills (by apoptosis) the precursors of the dendritic cells that induce the Th2 path and thus further
production of IL-4.
IFN-γ may eventually turn off the Th1 response that produced it.
Chemokines bind to receptors on the responding leukocyte. The receptors are transmembrane proteins with
the chemokine binding site exposed at the surface of the plasma membrane. CC chemokine receptors are
designated CCR.
With their different functions, we might expect that Th1 cells and Th2 cells would respond differently to
chemokines. And so they do.
Th1 cells express the chemokine receptor CCR5 (but not CCR3).
Th2 cells express the chemokine receptor CCR3 (but not CCR5).
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CCR3
One chemokine that binds to CCR3 is called eotaxin. It is secreted by epithelial cells and phagocytic cells in
regions where allergic reactions are occurring.
CCR3 is found on
Th2 cells
eosinophils
basophils
CCR5
CCR5 is found on
CCR5 also acts — along with the CD4 molecule — as a coreceptor for HIV-1, the retrovirus that causes
AIDS. This fact may explain
why destruction of the lymphoid tissue of the intestine occurs soon after HIV infection;
why certain HIV-infected men
with inherited mutations preventing the expression of CCR5 or
who produce high levels of the natural ligand for CCR5 (a chemokine designated CCL3L1,
which presumably competes with HIV for access to CCR5)
can tolerate their infection for long periods without progressing to a full-blown case of AIDS;
the collapse of cell-mediated immunity in the late stages of AIDS.
One striking illustration: an AIDS patient with leukemia was given a bone marrow transplant from a donor
whose cells expressed a nonfunctional version of CCR5. Two years later, the patient was not only cured of
his leukemia but of AIDS as well.
Another: Gene therapy in which samples of a patient's CD4+ T cells were treated in vitro so that their
CCR5 gene became nonfunctional [how it was done]. Expanded in culture and then returned to the donor,
five (of six) patients had their CD4+ T cell counts rebound.
Tfh Cells
Follicular helper T cells (Tfh) are
CD4+ helper T cells found in nests of
B cells — called follicles — in the
lymph nodes.
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The combined stimuli of antigen binding to their TCR and exposure to cytokines activate a transcription
factor called Bcl-6 (first identified in a B-cell lymphoma). Bcl-6 turns on a collection of genes which, among
other things, cause the Tfh cells to form an immunological synapse with those B cells expressing the antigen
fragments in class II histocompatibility molecules that match their TCR.
Several other pairs of ligands and their receptors stabilize the synapse, including the interaction between
CD28 on the Tfh cell and its ligand, B7, on the B cell [View].
undergo class switching with the synthesis of other antibody classes (except IgE);
undergo affinity maturation;
form antibody-secreting plasma cells and
memory B cells.
It is not yet certain whether Tfh cells represent a distinct class of Th cells or are simply a further stage in the
maturation of Th1, or Th2, or Th17 cells.
Th17 Cells
Th17 cells are a recently-identified subset of CD4+ T helper cells. They are found at the interfaces between
the external environment and the internal environment, e.g., skin and lining of the GI tract.
They probably start out like other "naive" Th cells, but when exposed to
they enter a pathway distinct from that of Th1, Th2, and Tfh cells. The combined stimuli of
activate a nuclear retinoid receptor designated RORγt. This is a transcription factor that turns on a collection
of genes which, among other things, leads to
the synthesis and secretion of IL-17 (giving the cells their name);
increased synthesis of the plasma membrane receptor for the interleukin IL-23. Interaction of IL-23
(perhaps secreted from nearby dendritic cells) with the receptor drives the rapid proliferation of the
Th17 cells.
Situated in the skin and the lining of the GI tract, Th17 cells are positioned to attack fungi and bacteria at
those locations. They do this by secreting defensins and recruiting scavenging cells, especially neutrophils,
to the site. The result: clearing away of the invaders with accompanying inflammation.
But inflammation is a double-edged sword. So it is not surprising that Th17 cells have been implicated as
potent effectors of such damaging inflammatory disorders as
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Summary Table
Master
Cytokine Effector Main Target Effector Pathological
Type Transcription
Stimulus Cytokine(s) Cells Targets/Functions Effects
Factor
Autoimmunity;
IFN-γ & Macrophages,
Th1 IL-12 & IL-2 T-bet Intracellular pathogens cell-mediated
TNF-β dendritic cells
allergies
Eosinophils, Asthma and
IL-4, IL-5
Th2 IL-4 GATA3 basophils, B Various helminths IgE-mediated
& IL-13
cells allergies
Class Switch
IL-21 &
Recombination and Autoimmune
Tfh IL-2 & others Bcl-6 either IL-4 B cells
Affinity Maturation of diseases?
or IFN-γ
antibodies
TGF-β plus
Extracellular bacteria
IL-6 IL-17, IL- Autoimmune
Th17 RORγt Neutrophils and fungi
Inhibited by 22 & IL-23 diseases
mediates inflammation
retinoic acid
TGF-β minus
IL-6 all the other
IL-10 & Immunosuppression;
pTreg Stimulated by Foxp3 types of T None?
TGF-β anti-inflammatory
retinoic acid cells
and IL-2
Welcome&Next Search
10 December 2015
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